2-189295688-C-T

Variant names:

• chr2-189295688-C-T
• rs4667276
• XM_011510573.4:c.-227+42187G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000747641.1(ENSG00000288866):​n.621-36592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,030 control chromosomes in the GnomAD database, including 26,145 homozygotes. 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: 𝑓 0.57 (26145 hom., cov: 32)
• Consequence: ENSG00000288866 ENST00000747641.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.86
• Publications: 3 publications found

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]

COL5A2 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome, classic type

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Ehlers-Danlos syndrome, classic type, 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ENSG00000288866 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000747641.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000288866	ENST00000747641.1		n.621-36592G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85895 AN: 151912 Hom.: 26137 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.565 AC: 85930 AN: 152030 Hom.: 26145 Cov.: 32 AF XY: 0.566 AC XY: 42054 AN XY: 74324

African (AFR) AF: 0.311 AC: 12877 AN: 41440

American (AMR) AF: 0.596 AC: 9105 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2277 AN: 3468

East Asian (EAS) AF: 0.715 AC: 3694 AN: 5168

South Asian (SAS) AF: 0.593 AC: 2860 AN: 4820

European-Finnish (FIN) AF: 0.656 AC: 6929 AN: 10568

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46041 AN: 67964

Other (OTH) AF: 0.594 AC: 1254 AN: 2112

Alfa AF: 0.637 Hom.: 98894

Bravo AF: 0.549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.086
DANN	Benign	0.55
PhyloP100		-3.9

Splicing

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

Other links and lift over

dbSNP: rs4667276; hg19: chr2-190160414;