rs9559814

chr13-110469136-A-Gchr13-110469136-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):c.2096-81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,492,644 control chromosomes in the GnomAD database, including 265,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (28263 hom., cov: 33)
  • Exomes 𝑓: 0.59 (237085 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 13-110469136-A-G is Benign according to our data. Variant chr13-110469136-A-G is described in ClinVar as [Benign]. Clinvar id is 1274675.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A2	NM_001846.4	c.2096-81A>G		intron_variant		ENST00000360467.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A2	ENST00000360467.7	c.2096-81A>G		intron_variant		5	NM_001846.4	P1
COL4A2	ENST00000494852.2	c.16-81A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91235 AN: 151996 Hom.: 28230 Cov.: 33

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.589 AC: 789142 AN: 1340530 Hom.: 237085 AF XY: 0.585 AC XY: 387239 AN XY: 661568

Gnomad4 AFR exome AF: 0.712

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.660

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.614

Gnomad4 OTH exome AF: 0.588

GnomAD4 genome AF: 0.600 AC: 91326 AN: 152114 Hom.: 28263 Cov.: 33 AF XY: 0.588 AC XY: 43742 AN XY: 74352

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.606

Alfa AF: 0.534 Hom.: 2723

Bravo AF: 0.607

Asia WGS AF: 0.401 AC: 1396 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	0.026
Dann	Benign	0.47

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: rs9559814; hg19: chr13-111121483; COSMIC: COSV64629152; COSMIC: COSV64629152;