rs1553512393

chr2-189034970-GA-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Moderate PM2 PP5

The NM_000393.5(COL5A2):c.4298del(p.Ile1433ThrfsTer43) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. I1433I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL5A2 NM_000393.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.32

Genes affected

COL5A2 (HGNC:2210): (collagen type V alpha 2 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0449 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-189034970-GA-G is Pathogenic according to our data. Variant chr2-189034970-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 518426.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A2	NM_000393.5	c.4298del	p.Ile1433ThrfsTer43	frameshift_variant	53/54	ENST00000374866.9
COL5A2	XM_011510573.4	c.4160del	p.Ile1387ThrfsTer43	frameshift_variant	56/57
COL5A2	XM_047443251.1	c.4160del	p.Ile1387ThrfsTer43	frameshift_variant	58/59
COL5A2	XM_047443252.1	c.4160del	p.Ile1387ThrfsTer43	frameshift_variant	57/58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A2	ENST00000374866.9	c.4298del	p.Ile1433ThrfsTer43	frameshift_variant	53/54	1	NM_000393.5	P1
COL5A2	ENST00000618828.1	c.3137del	p.Ile1046ThrfsTer43	frameshift_variant	46/47	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ehlers-Danlos syndrome, classic type Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553512393; hg19: chr2-189899696;