11-103154567-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001377.3(DYNC2H1):c.3419G>T(p.Gly1140Val) variant causes a missense change. The variant allele was found at a frequency of 0.000575 in 1,602,696 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001377.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.3419G>T | p.Gly1140Val | missense_variant | Exon 23 of 90 | ENST00000650373.2 | NP_001073932.1 | |
DYNC2H1 | NM_001377.3 | c.3419G>T | p.Gly1140Val | missense_variant | Exon 23 of 89 | ENST00000375735.7 | NP_001368.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.3419G>T | p.Gly1140Val | missense_variant | Exon 23 of 90 | NM_001080463.2 | ENSP00000497174.1 | |||
DYNC2H1 | ENST00000375735.7 | c.3419G>T | p.Gly1140Val | missense_variant | Exon 23 of 89 | 1 | NM_001377.3 | ENSP00000364887.2 |
Frequencies
GnomAD3 genomes AF: 0.000421 AC: 64AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000394 AC: 92AN: 233592Hom.: 0 AF XY: 0.000459 AC XY: 58AN XY: 126270
GnomAD4 exome AF: 0.000592 AC: 858AN: 1450522Hom.: 0 Cov.: 31 AF XY: 0.000593 AC XY: 427AN XY: 720442
GnomAD4 genome AF: 0.000421 AC: 64AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74416
ClinVar
Submissions by phenotype
Asphyxiating thoracic dystrophy 3 Uncertain:2
The DYNC2H1 c.3419G>T; p.Gly1140Val variant, to our knowledge, is not described in the medical literature but is reported as a variant of uncertain clinical significance in ClinVar (Variation ID: 302025). It is observed in the general population at an overall frequency of 0.04% (107/264972 alleles) in the Genome Aggregation Database. The glycine at codon 1140 is highly conserved, but computational algorithms (PolyPhen-2, SIFT) predict that this variant is tolerated. Due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty. -
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Short rib-polydactyly syndrome Uncertain:1
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Jeune thoracic dystrophy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at