rs7586

Variant names:

• chr2-189033772-C-T
• rs7586
• NM_000393.5:c.*298G>A

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.*298G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 396,392 control chromosomes in the GnomAD database, including 781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (473 hom., cov: 32)
  • Exomes 𝑓: 0.042 (308 hom.)
• Consequence: COL5A2 NM_000393.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0750
• 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=-0.78).
• BP6: Variant 2-189033772-C-T is Benign according to our data. Variant chr2-189033772-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 333126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 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.*298G>A		3_prime_UTR	Exon 54 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.*298G>A		3_prime_UTR	Exon 54 of 54	ENSP00000364000.3	P05997
	COL5A2	ENST00000858728.1		c.*298G>A		3_prime_UTR	Exon 54 of 54	ENSP00000528787.1
	COL5A2	ENST00000858729.1		c.*298G>A		3_prime_UTR	Exon 53 of 53	ENSP00000528788.1

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10435 AN: 151888 Hom.: 466 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.00405

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0482

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0679

GnomAD4 exome AF: 0.0418 AC: 10221 AN: 244386 Hom.: 308 Cov.: 2 AF XY: 0.0402 AC XY: 5183 AN XY: 128950

African (AFR) AF: 0.138 AC: 1106 AN: 8026

American (AMR) AF: 0.0461 AC: 488 AN: 10584

Ashkenazi Jewish (ASJ) AF: 0.0612 AC: 464 AN: 7586

East Asian (EAS) AF: 0.00470 AC: 69 AN: 14668

South Asian (SAS) AF: 0.0261 AC: 792 AN: 30324

European-Finnish (FIN) AF: 0.0438 AC: 504 AN: 11518

Middle Eastern (MID) AF: 0.0867 AC: 90 AN: 1038

European-Non Finnish (NFE) AF: 0.0413 AC: 6055 AN: 146584

Other (OTH) AF: 0.0465 AC: 653 AN: 14058

GnomAD4 genome AF: 0.0689 AC: 10467 AN: 152006 Hom.: 473 Cov.: 32 AF XY: 0.0683 AC XY: 5076 AN XY: 74308

African (AFR) AF: 0.138 AC: 5718 AN: 41424

American (AMR) AF: 0.0453 AC: 692 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0590 AC: 205 AN: 3472

East Asian (EAS) AF: 0.00406 AC: 21 AN: 5172

South Asian (SAS) AF: 0.0284 AC: 137 AN: 4822

European-Finnish (FIN) AF: 0.0482 AC: 508 AN: 10542

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0431 AC: 2929 AN: 67978

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0682 Hom.: 92

Bravo AF: 0.0721

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Ehlers-Danlos syndrome type 7A (1)
-	-	1	Ehlers-Danlos syndrome, classic type, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		0.075
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: rs7586; hg19: chr2-189898498;