chr3-49510719-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004393.6(DAG1):c.185C>T(p.Pro62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,614,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004393.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DAG1 | NM_004393.6 | c.185C>T | p.Pro62Leu | missense_variant | Exon 2 of 3 | ENST00000308775.7 | NP_004384.5 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152180Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000111 AC: 28AN: 251346Hom.: 0 AF XY: 0.000132 AC XY: 18AN XY: 135854
GnomAD4 exome AF: 0.0000951 AC: 139AN: 1461886Hom.: 0 Cov.: 75 AF XY: 0.0000935 AC XY: 68AN XY: 727244
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152298Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:3
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Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;C4511963:Autosomal recessive limb-girdle muscular dystrophy type 2P Uncertain:2Other:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 62 of the DAG1 protein (p.Pro62Leu). This variant is present in population databases (rs375938350, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 282776). 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 not expected to disrupt DAG1 protein function. 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. -
Variant interpreted as Uncertain significance and reported on 11-27-2017 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -
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Inborn genetic diseases Uncertain:1
The c.185C>T (p.P62L) alteration is located in exon 2 (coding exon 1) of the DAG1 gene. This alteration results from a C to T substitution at nucleotide position 185, causing the proline (P) at amino acid position 62 to be replaced by a leucine (L). 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