chr2-189052153-T-C

Variant names:

• chr2-189052153-T-C
• rs111609220
• NM_000393.5:c.2769+19A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000393.5(COL5A2):​c.2769+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.2769+19A>G		intron_variant	Intron 41 of 53	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.2631+19A>G		intron_variant	Intron 44 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.2631+19A>G		intron_variant	Intron 46 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.2631+19A>G		intron_variant	Intron 45 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.2769+19A>G		intron_variant	Intron 41 of 53	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.1608+19A>G		intron_variant	Intron 34 of 46	5		ENSP00000482184.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	21
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.41		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs111609220; hg19: chr2-189916879;