rs773864097
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_152490.5(B3GALNT2):c.1019A>G(p.Tyr340Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000156 in 1,602,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_152490.5 missense
Scores
Clinical Significance
Conservation
Publications
- muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
- autosomal recessive non-syndromic intellectual disabilityInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- muscle-eye-brain diseaseInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- muscular dystrophy-dystroglycanopathy, type AInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- intellectual disabilityInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000528 AC: 8AN: 151650Hom.: 0 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.0000373 AC: 9AN: 241348 AF XY: 0.0000154 show subpopulations
GnomAD4 exome AF: 0.0000117 AC: 17AN: 1450914Hom.: 0 Cov.: 33 AF XY: 0.0000125 AC XY: 9AN XY: 721292 show subpopulations
GnomAD4 genome AF: 0.0000528 AC: 8AN: 151650Hom.: 0 Cov.: 31 AF XY: 0.0000540 AC XY: 4AN XY: 74058 show subpopulations
ClinVar
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 Uncertain:2
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 340 of the B3GALNT2 protein (p.Tyr340Cys). This variant is present in population databases (rs773864097, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with B3GALNT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 579191). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
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Inborn genetic diseases Uncertain:1
The c.1019A>G (p.Y340C) alteration is located in exon 8 (coding exon 8) of the B3GALNT2 gene. This alteration results from a A to G substitution at nucleotide position 1019, causing the tyrosine (Y) at amino acid position 340 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at