chr2-189057312-G-T

Variant names:

• chr2-189057312-G-T
• NM_000393.5:c.2337+8C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000393.5(COL5A2):​c.2337+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL5A2 NM_000393.5 splice_region, intron
• Scores: Splicing: ADA: 0.00006331
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.2337+8C>A		splice_region_variant, intron_variant	Intron 34 of 53	ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.2199+8C>A		splice_region_variant, intron_variant	Intron 37 of 56		XP_011508875.1
COL5A2	XM_047443251.1	c.2199+8C>A		splice_region_variant, intron_variant	Intron 39 of 58		XP_047299207.1
COL5A2	XM_047443252.1	c.2199+8C>A		splice_region_variant, intron_variant	Intron 38 of 57		XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.2337+8C>A		splice_region_variant, intron_variant	Intron 34 of 53	1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.1176+8C>A		splice_region_variant, intron_variant	Intron 27 of 46	5		ENSP00000482184.1
COL5A2	ENST00000470524.2	n.443+8C>A		splice_region_variant, intron_variant	Intron 7 of 7	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 64540 Hom.: 0 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000163 AC: 138 AN: 844650 Hom.: 0 Cov.: 18 AF XY: 0.000161 AC XY: 70 AN XY: 434192

Gnomad4 AFR exome AF: 0.0000497

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000164

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000517

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000213

Gnomad4 OTH exome AF: 0.0000259

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 64568 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 31088

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000063
dbscSNV1_RF	Benign	0.0
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-189922038;