rs2296851

Positions:

• chr13-110485908-G-A

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.3207+72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,581,824 control chromosomes in the GnomAD database, including 14,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1400 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13149 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0290

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=-0.87).
• BP6: Variant 13-110485908-G-A is Benign according to our data. Variant chr13-110485908-G-A is described in ClinVar as [Benign]. Clinvar id is 1229583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.3207+72G>A		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.3207+72G>A		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000650225.1	n.862+72G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20623 AN: 152066 Hom.: 1397 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.134 AC: 191168 AN: 1429640 Hom.: 13149 AF XY: 0.133 AC XY: 94103 AN XY: 709254

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0996

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.136 AC: 20645 AN: 152184 Hom.: 1400 Cov.: 32 AF XY: 0.135 AC XY: 10068 AN XY: 74404

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.125

Alfa AF: 0.132 Hom.: 2405

Bravo AF: 0.138

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.61

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: rs2296851; hg19: chr13-111138255; COSMIC: COSV64636527; COSMIC: COSV64636527;