rs2281968

Variant names:

• chr13-110501813-G-A
• rs2281968
• NM_001846.4:c.3877+29G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110501813-G-A
• chr13-110501813-G-C

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.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:3
• Conservation: PhyloP100: -1.95
• Publications: 12 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

ENSG00000289010 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1182480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3877+29G>A		intron_variant	Intron 41 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3877+29G>A		intron_variant	Intron 41 of 47	5	NM_001846.4	ENSP00000353654.5

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

GnomAD2 exomes AF: 0.566 AC: 137807 AN: 243268 AF XY: 0.578

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 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

African (AFR) AF: 0.486 AC: 16010 AN: 32962

American (AMR) AF: 0.429 AC: 18639 AN: 43448

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 14891 AN: 25976

East Asian (EAS) AF: 0.311 AC: 12326 AN: 39606

South Asian (SAS) AF: 0.629 AC: 53591 AN: 85142

European-Finnish (FIN) AF: 0.665 AC: 35325 AN: 53114

Middle Eastern (MID) AF: 0.671 AC: 3847 AN: 5732

European-Non Finnish (NFE) AF: 0.617 AC: 680728 AN: 1102970

Other (OTH) AF: 0.594 AC: 35563 AN: 59904

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

African (AFR) AF: 0.486 AC: 20129 AN: 41424

American (AMR) AF: 0.507 AC: 7744 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1953 AN: 3466

East Asian (EAS) AF: 0.352 AC: 1810 AN: 5140

South Asian (SAS) AF: 0.632 AC: 3043 AN: 4812

European-Finnish (FIN) AF: 0.660 AC: 6978 AN: 10578

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41694 AN: 67924

Other (OTH) AF: 0.574 AC: 1209 AN: 2106

Alfa AF: 0.587 Hom.: 8590

Bravo AF: 0.541

Asia WGS AF: 0.525 AC: 1827 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Porencephaly 2 Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.54
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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