rs6434317

Variant names:

• chr2-189071961-T-A
• rs6434317
• NM_000393.5:c.1158+79A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-189071961-T-A
• chr2-189071961-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000393.5(COL5A2):​c.1158+79A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.671
• Publications: 8 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.1158+79A>T		intron_variant	Intron 18 of 53	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.1020+79A>T		intron_variant	Intron 21 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.1020+79A>T		intron_variant	Intron 23 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.1020+79A>T		intron_variant	Intron 22 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.1158+79A>T		intron_variant	Intron 18 of 53	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.359-5528A>T		intron_variant	Intron 15 of 46	5		ENSP00000482184.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 808598 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 419946

African (AFR) AF: 0.00 AC: 0 AN: 19774

American (AMR) AF: 0.00 AC: 0 AN: 32056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20962

East Asian (EAS) AF: 0.00 AC: 0 AN: 33842

South Asian (SAS) AF: 0.00 AC: 0 AN: 62392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3770

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 548300

Other (OTH) AF: 0.00 AC: 0 AN: 38468

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 23099

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		-0.67

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: rs6434317; hg19: chr2-189936687;