rs999144463

Positions:

• chr2-189057312-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000393.5(COL5A2):​c.2337+8C>T 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000072 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL5A2 NM_000393.5 splice_region, intron
• Scores: Splicing: ADA: 0.00006271
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-189057312-G-A is Benign according to our data. Variant chr2-189057312-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 459736.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL5A2	NM_000393.5	c.2337+8C>T		splice_region_variant, intron_variant		ENST00000374866.9
COL5A2	XM_011510573.4	c.2199+8C>T		splice_region_variant, intron_variant
COL5A2	XM_047443251.1	c.2199+8C>T		splice_region_variant, intron_variant
COL5A2	XM_047443252.1	c.2199+8C>T		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL5A2	ENST00000374866.9	c.2337+8C>T		splice_region_variant, intron_variant		1	NM_000393.5	P1
COL5A2	ENST00000618828.1	c.1176+8C>T		splice_region_variant, intron_variant		5
COL5A2	ENST00000470524.2	n.443+8C>T		splice_region_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 106 AN: 64300 Hom.: 0 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00181

Gnomad ASJ AF: 0.00122

Gnomad EAS AF: 0.00105

Gnomad SAS AF: 0.000542

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000722 AC: 61 AN: 844994 Hom.: 0 Cov.: 18 AF XY: 0.0000645 AC XY: 28 AN XY: 434324

Gnomad4 AFR exome AF: 0.000248

Gnomad4 AMR exome AF: 0.000586

Gnomad4 ASJ exome AF: 0.000109

Gnomad4 EAS exome AF: 0.000123

Gnomad4 SAS exome AF: 0.000138

Gnomad4 FIN exome AF: 0.0000549

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.0000519

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00165 AC: 106 AN: 64328 Hom.: 0 Cov.: 17 AF XY: 0.00178 AC XY: 55 AN XY: 30966

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00181

Gnomad4 ASJ AF: 0.00122

Gnomad4 EAS AF: 0.00105

Gnomad4 SAS AF: 0.000546

Gnomad4 FIN AF: 0.00434

Gnomad4 NFE AF: 0.00203

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000801 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome, classic type, 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 12, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs999144463; hg19: chr2-189922038; COSMIC: COSV66408747;