chr9-127935765-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_003863.4(DPM2):āc.212A>Gā(p.Tyr71Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,020 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 (ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y71Y) has been classified as Benign.
Frequency
Consequence
NM_003863.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPM2 | NM_003863.4 | c.212A>G | p.Tyr71Cys | missense_variant | 4/4 | ENST00000314392.13 | |
DPM2 | NM_001378437.1 | c.122A>G | p.Tyr41Cys | missense_variant | 3/3 | ||
DPM2 | NR_165631.1 | n.369A>G | non_coding_transcript_exon_variant | 4/4 | |||
DPM2 | NR_165632.1 | n.53A>G | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPM2 | ENST00000314392.13 | c.212A>G | p.Tyr71Cys | missense_variant | 4/4 | 1 | NM_003863.4 | P1 | |
ENST00000592240.5 | n.143+1120T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251214Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135804
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1460906Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 726794
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
Congenital muscular dystrophy with intellectual disability and severe epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 04, 2022 | This variant has not been reported in the literature in individuals affected with DPM2-related conditions. This variant is present in population databases (rs776591740, gnomAD 0.05%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 71 of the DPM2 protein (p.Tyr71Cys). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at