rs373288848
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_000393.5(COL5A2):c.3209G>A(p.Arg1070His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1070C) has been classified as Likely benign.
Frequency
Consequence
NM_000393.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A2 | NM_000393.5 | c.3209G>A | p.Arg1070His | missense_variant | 46/54 | ENST00000374866.9 | |
COL5A2 | XM_011510573.4 | c.3071G>A | p.Arg1024His | missense_variant | 49/57 | ||
COL5A2 | XM_047443251.1 | c.3071G>A | p.Arg1024His | missense_variant | 51/59 | ||
COL5A2 | XM_047443252.1 | c.3071G>A | p.Arg1024His | missense_variant | 50/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A2 | ENST00000374866.9 | c.3209G>A | p.Arg1070His | missense_variant | 46/54 | 1 | NM_000393.5 | P1 | |
COL5A2 | ENST00000618828.1 | c.2048G>A | p.Arg683His | missense_variant | 39/47 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251294Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135838
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461302Hom.: 0 Cov.: 30 AF XY: 0.0000261 AC XY: 19AN XY: 727034
GnomAD4 genome AF: 0.000164 AC: 25AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74428
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2023 | Identified by exome sequencing in one individual with a conotruncal heart defect who was compound heterozygous for another variant in the COL5A2 gene (Jin et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28991257) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 12, 2014 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at