Submissions for variant NM_000283.4(PDE6B):c.2152G>A (p.Asp718Asn)

dbSNP: rs150639487

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000297097	SCV000340729	uncertain significance	not provided	2016-03-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000277605	SCV000450826	uncertain significance	Congenital stationary night blindness autosomal dominant 2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000332675	SCV000450827	uncertain significance	Retinitis pigmentosa	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000297097	SCV001154144	uncertain significance	not provided	2019-05-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000297097	SCV001510447	pathogenic	not provided	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 718 of the PDE6B protein (p.Asp718Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal recessive PDE6B-related conditions (PMID: 34906470, 36819107; Invitae). ClinVar contains an entry for this variant (Variation ID: 287073). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PDE6B protein function with a positive predictive value of 95%. This variant disrupts the p.Asp718 amino acid residue in PDE6B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30998820; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000332675	SCV001950312	uncertain significance	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	The p.Asp718Asn variant in PDE6B was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV002286728	SCV002577574	uncertain significance	Retinitis pigmentosa 40	2022-03-28	criteria provided, single submitter	clinical testing	PM1, PM2, PP3, PP4 We detected this variant in homozygous state in a patient with retinitis pigmentosa.