rs2296853

Variant names:

• chr13-110484893-A-G
• rs2296853
• NM_001846.4:c.2903-12A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-110484893-A-G
• chr13-110484893-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.2903-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,601,718 control chromosomes in the GnomAD database, including 22,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1872 hom., cov: 31)
  • Exomes 𝑓: 0.16 (20418 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Scores: Splicing: ADA: 0.00002152
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.147
• Publications: 7 publications found

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]

COL4A2 Gene-Disease associations (from GenCC):

• porencephaly 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• COL4A1 or COL4A2-related cerebral small vessel disease

  Inheritance: AD Classification: MODERATE Submitted by: Illumina
• familial porencephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-110484893-A-G is Benign according to our data. Variant chr13-110484893-A-G is described in ClinVar as Benign. ClinVar VariationId is 311153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2903-12A>G		intron_variant	Intron 32 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2903-12A>G		intron_variant	Intron 32 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21181 AN: 151796 Hom.: 1868 Cov.: 31

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.159 AC: 38469 AN: 242686 AF XY: 0.156

Gnomad AFR exome AF: 0.0393

Gnomad AMR exome AF: 0.231

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.157

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.163 AC: 236686 AN: 1449800 Hom.: 20418 Cov.: 33 AF XY: 0.161 AC XY: 116103 AN XY: 720514

African (AFR) AF: 0.0371 AC: 1224 AN: 32954

American (AMR) AF: 0.228 AC: 9866 AN: 43184

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 4967 AN: 25430

East Asian (EAS) AF: 0.185 AC: 7330 AN: 39524

South Asian (SAS) AF: 0.103 AC: 8763 AN: 85278

European-Finnish (FIN) AF: 0.158 AC: 8348 AN: 52898

Middle Eastern (MID) AF: 0.135 AC: 768 AN: 5696

European-Non Finnish (NFE) AF: 0.168 AC: 185885 AN: 1105126

Other (OTH) AF: 0.160 AC: 9535 AN: 59710

GnomAD4 genome AF: 0.139 AC: 21188 AN: 151918 Hom.: 1872 Cov.: 31 AF XY: 0.141 AC XY: 10468 AN XY: 74264

African (AFR) AF: 0.0427 AC: 1768 AN: 41448

American (AMR) AF: 0.233 AC: 3565 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3464

East Asian (EAS) AF: 0.167 AC: 854 AN: 5104

South Asian (SAS) AF: 0.0985 AC: 474 AN: 4810

European-Finnish (FIN) AF: 0.169 AC: 1787 AN: 10562

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11553 AN: 67930

Other (OTH) AF: 0.154 AC: 325 AN: 2108

Alfa AF: 0.134 Hom.: 813

Bravo AF: 0.140

Asia WGS AF: 0.111 AC: 386 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 02, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Porencephaly 2 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.49
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0040
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

Other links and lift over

dbSNP: rs2296853; hg19: chr13-111137240; COSMIC: COSV100847290;