rs6434312

Variant names:

• chr2-189043211-A-G
• rs6434312
• NM_000393.5:c.3411T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-189043211-A-G
• chr2-189043211-A-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000393.5(COL5A2):​c.3411T>C​(p.Gly1137Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 1,613,866 control chromosomes in the GnomAD database, including 762,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70265 hom., cov: 30)
  • Exomes 𝑓: 0.97 (692073 hom.)
• Consequence: COL5A2 NM_000393.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.09
• Publications: 22 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-189043211-A-G is Benign according to our data. Variant chr2-189043211-A-G is described in ClinVar as Benign. ClinVar VariationId is 1164098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 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.3411T>C	p.Gly1137Gly	synonymous	Exon 48 of 54	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.3411T>C	p.Gly1137Gly	synonymous	Exon 48 of 54	ENSP00000364000.3	P05997
	COL5A2	ENST00000858728.1		c.3408T>C	p.Gly1136Gly	synonymous	Exon 48 of 54	ENSP00000528787.1
	COL5A2	ENST00000858729.1		c.3303T>C	p.Gly1101Gly	synonymous	Exon 47 of 53	ENSP00000528788.1

Frequencies

GnomAD3 genomes AF: 0.960 AC: 146094 AN: 152136 Hom.: 70210 Cov.: 30

Gnomad AFR AF: 0.947

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.919

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.959

GnomAD2 exomes AF: 0.950 AC: 238595 AN: 251182 AF XY: 0.956

Gnomad AFR exome AF: 0.949

Gnomad AMR exome AF: 0.842

Gnomad ASJ exome AF: 0.972

Gnomad EAS exome AF: 0.912

Gnomad FIN exome AF: 0.950

Gnomad NFE exome AF: 0.981

Gnomad OTH exome AF: 0.957

GnomAD4 exome AF: 0.973 AC: 1421624 AN: 1461614 Hom.: 692073 Cov.: 47 AF XY: 0.973 AC XY: 707732 AN XY: 727110

African (AFR) AF: 0.946 AC: 31679 AN: 33474

American (AMR) AF: 0.849 AC: 37973 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 25403 AN: 26132

East Asian (EAS) AF: 0.886 AC: 35144 AN: 39684

South Asian (SAS) AF: 0.972 AC: 83824 AN: 86222

European-Finnish (FIN) AF: 0.953 AC: 50926 AN: 53410

Middle Eastern (MID) AF: 0.966 AC: 5557 AN: 5752

European-Non Finnish (NFE) AF: 0.983 AC: 1092560 AN: 1111852

Other (OTH) AF: 0.970 AC: 58558 AN: 60384

GnomAD4 genome AF: 0.960 AC: 146207 AN: 152252 Hom.: 70265 Cov.: 30 AF XY: 0.959 AC XY: 71359 AN XY: 74446

African (AFR) AF: 0.947 AC: 39345 AN: 41544

American (AMR) AF: 0.919 AC: 14050 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3385 AN: 3472

East Asian (EAS) AF: 0.910 AC: 4705 AN: 5170

South Asian (SAS) AF: 0.972 AC: 4683 AN: 4820

European-Finnish (FIN) AF: 0.948 AC: 10063 AN: 10614

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.981 AC: 66750 AN: 68024

Other (OTH) AF: 0.960 AC: 2027 AN: 2112

Alfa AF: 0.969 Hom.: 113534

Bravo AF: 0.954

Asia WGS AF: 0.958 AC: 3333 AN: 3478

EpiCase AF: 0.979

EpiControl AF: 0.977

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Ehlers-Danlos syndrome, classic type, 1 (1)
-	-	1	Ehlers-Danlos syndrome, classic type, 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.8
DANN	Benign	0.50
PhyloP100		1.1
Mutation Taster		=77/23	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: rs6434312; hg19: chr2-189907937; COSMIC: COSV66412801;