rs2281968

chr13-110501813-G-Achr13-110501813-G-C

Variant summary

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

The NM_001846.4(COL4A2):c.3877+29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 1,600,774 control chromosomes in the GnomAD database, including 289,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24404 hom., cov: 30)
  • Exomes 𝑓: 0.60 (265206 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.95

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 13-110501813-G-A is Benign according to our data. Variant chr13-110501813-G-A is described in ClinVar as [Benign]. Clinvar id is 1182480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110501813-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.3877+29G>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.3877+29G>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000650225.1	n.1532+29G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85262 AN: 151802 Hom.: 24400 Cov.: 30

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.577

GnomAD3 exomes AF: 0.566 AC: 137807 AN: 243268 Hom.: 40274 AF XY: 0.578 AC XY: 76539 AN XY: 132324

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.573

Gnomad EAS exome AF: 0.357

Gnomad SAS exome AF: 0.633

Gnomad FIN exome AF: 0.665

Gnomad NFE exome AF: 0.618

Gnomad OTH exome AF: 0.604

GnomAD4 exome AF: 0.601 AC: 870920 AN: 1448854 Hom.: 265206 Cov.: 27 AF XY: 0.603 AC XY: 435230 AN XY: 721386

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.594

GnomAD4 genome AF: 0.562 AC: 85306 AN: 151920 Hom.: 24404 Cov.: 30 AF XY: 0.562 AC XY: 41708 AN XY: 74244

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.574

Alfa AF: 0.585 Hom.: 4886

Bravo AF: 0.541

Asia WGS AF: 0.525 AC: 1827 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Porencephaly 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.47
Dann	Benign	0.54

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: rs2281968; hg19: chr13-111154160; COSMIC: COSV64626297; COSMIC: COSV64626297;