Submissions for variant NM_013382.7(POMT2):c.1712dup (p.Ile572fs)

dbSNP: rs780725241

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001009061	SCV001168871	likely pathogenic	not provided	2018-09-26	criteria provided, single submitter	clinical testing	The c.1712dupC variant in the POMT2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The 1712dupC variant causes a frameshift starting with codon Isoleucine 572, changes this amino acid to a Tyrosine residue, and creates a premature Stop codon at position 13 of the new reading frame, denoted p.Ile572TyrfsX13. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The 1712dupC variant is observed in 1/246254 (0.0004%) alleles in large population cohorts (Lek et al., 2016). We interpret 1712dupC as a likely pathogenic variant.
Ambry Genetics	RCV002551722	SCV003556216	pathogenic	Inborn genetic diseases	2021-06-18	criteria provided, single submitter	clinical testing	The c.1712dupC (p.I572Yfs*13) alteration, located in exon 16 (coding exon 16) of the POMT2 gene, consists of a duplication of C at position 1712, causing a translational frameshift with a predicted alternate stop codon after 13 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from the Genome Aggregation Database (gnomAD) database, the POMT2 c.1712dupC alteration was observed in <0.01% (1/251468) of total alleles studied. Based on the available evidence, this alteration is classified as pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003411949	SCV004109133	likely pathogenic	POMT2-related condition	2022-08-18	criteria provided, single submitter	clinical testing	The POMT2 c.1712dupC variant is predicted to result in a frameshift and premature protein termination (p.Ile572Tyrfs*13). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in POMT2 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Baylor Genetics	RCV003473558	SCV004204094	likely pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2	2023-10-01	criteria provided, single submitter	clinical testing
Invitae	RCV003769416	SCV004604013	pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2; Autosomal recessive limb-girdle muscular dystrophy type 2N	2024-01-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile572Tyrfs*13) in the POMT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMT2 are known to be pathogenic (PMID: 15894594). This variant is present in population databases (rs780725241, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with POMT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 817839). For these reasons, this variant has been classified as Pathogenic.