rs6414122

Positions:

• chr2-189060822-T-A
• chr2-189060822-T-C
• chr2-189060822-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000393.5(COL5A2):​c.2032-39A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 1,548,112 control chromosomes in the GnomAD database, including 734,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.96 (69898 hom., cov: 31)
  • Exomes 𝑓: 0.98 (664191 hom.)
• Consequence: COL5A2 NM_000393.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.523

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-189060822-T-A is Benign according to our data. Variant chr2-189060822-T-A is described in ClinVar as [Benign]. Clinvar id is 255997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A2	NM_000393.5	c.2032-39A>T		intron_variant		ENST00000374866.9	NP_000384.2
COL5A2	XM_011510573.4	c.1894-39A>T		intron_variant			XP_011508875.1
COL5A2	XM_047443251.1	c.1894-39A>T		intron_variant			XP_047299207.1
COL5A2	XM_047443252.1	c.1894-39A>T		intron_variant			XP_047299208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A2	ENST00000374866.9	c.2032-39A>T		intron_variant		1	NM_000393.5	ENSP00000364000.3
COL5A2	ENST00000618828.1	c.871-39A>T		intron_variant		5		ENSP00000482184.1
COL5A2	ENST00000470524.2	n.138-39A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145690 AN: 152154 Hom.: 69851 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.946

GnomAD3 exomes AF: 0.957 AC: 238822 AN: 249640 Hom.: 114604 AF XY: 0.962 AC XY: 130067 AN XY: 135180

Gnomad AFR exome AF: 0.919

Gnomad AMR exome AF: 0.840

Gnomad ASJ exome AF: 0.972

Gnomad EAS exome AF: 0.970

Gnomad SAS exome AF: 0.972

Gnomad FIN exome AF: 0.998

Gnomad NFE exome AF: 0.982

Gnomad OTH exome AF: 0.961

GnomAD4 exome AF: 0.975 AC: 1361062 AN: 1395840 Hom.: 664191 Cov.: 22 AF XY: 0.976 AC XY: 681781 AN XY: 698704

Gnomad4 AFR exome AF: 0.917

Gnomad4 AMR exome AF: 0.847

Gnomad4 ASJ exome AF: 0.972

Gnomad4 EAS exome AF: 0.938

Gnomad4 SAS exome AF: 0.973

Gnomad4 FIN exome AF: 0.998

Gnomad4 NFE exome AF: 0.983

Gnomad4 OTH exome AF: 0.971

GnomAD4 genome AF: 0.957 AC: 145794 AN: 152272 Hom.: 69898 Cov.: 31 AF XY: 0.958 AC XY: 71332 AN XY: 74456

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.975

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.982

Gnomad4 OTH AF: 0.947

Alfa AF: 0.968 Hom.: 13090

Bravo AF: 0.947

Asia WGS AF: 0.970 AC: 3375 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.71
BranchPoint Hunter		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs6414122; hg19: chr2-189925548;