chr2-189062913-AGCTCCCT-A

Position:

• chr2-189062913-AGCTCCCT-A

Variant summary

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

The ENST00000374866.9(COL5A2):​c.1924-2_1928del variant causes a splice acceptor, coding sequence 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).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL5A2 ENST00000374866.9 splice_acceptor, coding_sequence
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.91

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: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.011777778 fraction of the gene. Cryptic splice site detected, with MaxEntScore 4.5, offset of -26, new splice context is: tactatttaaattatcatAGact. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-189062913-AGCTCCCT-A is Pathogenic according to our data. Variant chr2-189062913-AGCTCCCT-A is described in ClinVar as [Pathogenic]. Clinvar id is 17196.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.1924-2_1928del		splice_acceptor_variant, coding_sequence_variant	29/54	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.1786-2_1790del		splice_acceptor_variant, coding_sequence_variant	32/57		XP_011508875.1
COL5A2	XM_047443251.1	c.1786-2_1790del		splice_acceptor_variant, coding_sequence_variant	34/59		XP_047299207.1
COL5A2	XM_047443252.1	c.1786-2_1790del		splice_acceptor_variant, coding_sequence_variant	33/58		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.1924-2_1928del		splice_acceptor_variant, coding_sequence_variant	29/54	1	NM_000393.5	ENSP00000364000	P1
COL5A2	ENST00000618828.1	c.763-2_767del		splice_acceptor_variant, coding_sequence_variant	22/47	5		ENSP00000482184
COL5A2	ENST00000470524.2	n.30-2_34del		splice_acceptor_variant, non_coding_transcript_exon_variant	2/8	5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

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

Feb 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs786205103; hg19: chr2-189927639;