rs12693526

Variant names:

• chr2-189036569-G-A
• rs12693526
• NM_000393.5:c.4113+47C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-189036569-G-A
• chr2-189036569-G-C
• chr2-189036569-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000393.5(COL5A2):​c.4113+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 1,432,150 control chromosomes in the GnomAD database, including 438,191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (39695 hom., cov: 32)
  • Exomes 𝑓: 0.79 (398496 hom.)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.271

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-189036569-G-A is Benign according to our data. Variant chr2-189036569-G-A is described in ClinVar as [Benign]. Clinvar id is 256004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.4113+47C>T		intron_variant	Intron 52 of 53	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.3975+47C>T		intron_variant	Intron 55 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.3975+47C>T		intron_variant	Intron 57 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.3975+47C>T		intron_variant	Intron 56 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.4113+47C>T		intron_variant	Intron 52 of 53	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.2952+47C>T		intron_variant	Intron 45 of 46	5		ENSP00000482184.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108277 AN: 151826 Hom.: 39682 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.689

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.709

GnomAD3 exomes AF: 0.733 AC: 151438 AN: 206528 Hom.: 56351 AF XY: 0.737 AC XY: 83026 AN XY: 112646

Gnomad AFR exome AF: 0.521

Gnomad AMR exome AF: 0.643

Gnomad ASJ exome AF: 0.717

Gnomad EAS exome AF: 0.733

Gnomad SAS exome AF: 0.665

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.799

Gnomad OTH exome AF: 0.738

GnomAD4 exome AF: 0.785 AC: 1005214 AN: 1280206 Hom.: 398496 Cov.: 18 AF XY: 0.782 AC XY: 503705 AN XY: 643788

Gnomad4 AFR exome AF: 0.519

Gnomad4 AMR exome AF: 0.643

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.665

Gnomad4 SAS exome AF: 0.665

Gnomad4 FIN exome AF: 0.815

Gnomad4 NFE exome AF: 0.815

Gnomad4 OTH exome AF: 0.760

GnomAD4 genome AF: 0.713 AC: 108327 AN: 151944 Hom.: 39695 Cov.: 32 AF XY: 0.712 AC XY: 52897 AN XY: 74296

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.709

Alfa AF: 0.727 Hom.: 5219

Bravo AF: 0.694

Asia WGS AF: 0.653 AC: 2268 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.27
DANN	Benign	0.27

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: rs12693526; hg19: chr2-189901295; COSMIC: COSV66412027;