chr17-63833149-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001098426.2(SMARCD2):āc.1462A>Gā(p.Asn488Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,608,416 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 ). Synonymous variant affecting the same amino acid position (i.e. N488N) has been classified as Likely benign.
Frequency
Consequence
NM_001098426.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMARCD2 | NM_001098426.2 | c.1462A>G | p.Asn488Asp | missense_variant | 12/13 | ENST00000448276.7 | |
SMARCD2 | NM_001330440.2 | c.1318A>G | p.Asn440Asp | missense_variant | 12/13 | ||
SMARCD2 | NM_001330439.1 | c.1237A>G | p.Asn413Asp | missense_variant | 12/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMARCD2 | ENST00000448276.7 | c.1462A>G | p.Asn488Asp | missense_variant | 12/13 | 1 | NM_001098426.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000419 AC: 1AN: 238858Hom.: 0 AF XY: 0.00000773 AC XY: 1AN XY: 129374
GnomAD4 exome AF: 0.00000549 AC: 8AN: 1456260Hom.: 0 Cov.: 33 AF XY: 0.00000553 AC XY: 4AN XY: 723902
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2021 | This sequence change replaces asparagine with aspartic acid at codon 488 of the SMARCD2 protein (p.Asn488Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with SMARCD2-related conditions. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at