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. The variant received -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
• Publications: 6 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000393.5. 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
	COL5A2	NM_000393.5	MANE Select	c.4113+47C>T		intron	N/A	NP_000384.2	P05997

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A2	ENST00000374866.9	TSL:1 MANE Select	c.4113+47C>T		intron	N/A	ENSP00000364000.3	P05997
	COL5A2	ENST00000858728.1		c.4110+47C>T		intron	N/A	ENSP00000528787.1
	COL5A2	ENST00000858729.1		c.4005+47C>T		intron	N/A	ENSP00000528788.1

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

GnomAD2 exomes AF: 0.733 AC: 151438 AN: 206528 AF XY: 0.737

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 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

African (AFR) AF: 0.519 AC: 14638 AN: 28194

American (AMR) AF: 0.643 AC: 26894 AN: 41846

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 17736 AN: 24514

East Asian (EAS) AF: 0.665 AC: 23594 AN: 35482

South Asian (SAS) AF: 0.665 AC: 52360 AN: 78722

European-Finnish (FIN) AF: 0.815 AC: 40259 AN: 49400

Middle Eastern (MID) AF: 0.645 AC: 2842 AN: 4404

European-Non Finnish (NFE) AF: 0.815 AC: 786040 AN: 963914

Other (OTH) AF: 0.760 AC: 40851 AN: 53730

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

African (AFR) AF: 0.534 AC: 22107 AN: 41394

American (AMR) AF: 0.691 AC: 10548 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2503 AN: 3462

East Asian (EAS) AF: 0.726 AC: 3751 AN: 5164

South Asian (SAS) AF: 0.673 AC: 3245 AN: 4820

European-Finnish (FIN) AF: 0.822 AC: 8708 AN: 10592

Middle Eastern (MID) AF: 0.690 AC: 200 AN: 290

European-Non Finnish (NFE) AF: 0.810 AC: 55042 AN: 67948

Other (OTH) AF: 0.709 AC: 1494 AN: 2108

Alfa AF: 0.748 Hom.: 11502

Bravo AF: 0.694

Asia WGS AF: 0.653 AC: 2268 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.27
DANN	Benign	0.27
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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