11-103192133-T-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP5_Moderate
The NM_001080463.2(DYNC2H1):āc.7577T>Gā(p.Ile2526Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000071 in 1,549,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I2526V) has been classified as Likely benign.
Frequency
Consequence
NM_001080463.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.7577T>G | p.Ile2526Ser | missense_variant | 47/90 | ENST00000650373.2 | |
DYNC2H1 | NM_001377.3 | c.7577T>G | p.Ile2526Ser | missense_variant | 47/89 | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000650373.2 | c.7577T>G | p.Ile2526Ser | missense_variant | 47/90 | NM_001080463.2 | A1 | ||
DYNC2H1 | ENST00000375735.7 | c.7577T>G | p.Ile2526Ser | missense_variant | 47/89 | 1 | NM_001377.3 | P3 | |
DYNC2H1 | ENST00000334267.11 | c.2205+57714T>G | intron_variant | 1 | |||||
DYNC2H1 | ENST00000649323.1 | c.*5101T>G | 3_prime_UTR_variant, NMD_transcript_variant | 45/51 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000644 AC: 9AN: 1397070Hom.: 0 Cov.: 30 AF XY: 0.00000725 AC XY: 5AN XY: 689780
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
Asphyxiating thoracic dystrophy 3 Pathogenic:2
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
DYNC2H1-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 01, 2023 | The DYNC2H1 c.7577T>G variant is predicted to result in the amino acid substitution p.Ile2526Ser. This variant has been reported in fetuses affected with short rib-polydactyly syndrome (Ellard et al 2015. PubMed ID: 24961629; Table S2 in Zhang W et al 2017. PubMed ID: 29068549). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Based on the available evidence, this variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at