Submissions for variant NM_001371928.1(AHDC1):c.1122dup (p.Gly375fs)

dbSNP: rs749294057

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000190360	SCV000243810	pathogenic	not provided	2023-04-10	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 1229 amino acids are replaced with 2 different amino acids; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27148574, 31812316, 33644933, 33372375)
Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli	RCV001420216	SCV001622636	likely pathogenic	See cases	2021-04-26	criteria provided, single submitter	clinical testing	PVS1_strong;PM2_supporting;PM6_moderate
Mendelics	RCV002247613	SCV002516852	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV000190360	SCV002568831	pathogenic	not provided		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000190360	SCV004291774	pathogenic	not provided	2023-11-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly375Argfs*3) in the AHDC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AHDC1 are known to be pathogenic (PMID: 24791903, 27148574). 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 premature translational stop signal has been observed in individual(s) with AHDC1-related conditions (PMID: 27148574, 33644933). ClinVar contains an entry for this variant (Variation ID: 208155). For these reasons, this variant has been classified as Pathogenic.
Laboratory of Human Genetics, Universidade de São Paulo	RCV001563685	SCV005201024	pathogenic	AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome	2024-06-21	criteria provided, single submitter	clinical testing	PS4, PVS1, PM2
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV001563685	SCV001480342	pathogenic	AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome		no assertion criteria provided	clinical testing