chr13-110357296-G-A

Variant names:

• chr13-110357296-G-A
• rs12876517
• NM_001846.4:c.100-176G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001846.4(COL4A2):​c.100-176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,914 control chromosomes in the GnomAD database, including 22,475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (22475 hom., cov: 31)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.864
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 13-110357296-G-A is Benign according to our data. Variant chr13-110357296-G-A is described in ClinVar as [Benign]. Clinvar id is 1293746.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.100-176G>A		intron_variant	Intron 3 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.100-176G>A		intron_variant	Intron 3 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79747 AN: 151796 Hom.: 22459 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.525 AC: 79784 AN: 151914 Hom.: 22475 Cov.: 31 AF XY: 0.525 AC XY: 39007 AN XY: 74258

African (AFR) AF: 0.296 AC: 12276 AN: 41412

American (AMR) AF: 0.626 AC: 9566 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1889 AN: 3468

East Asian (EAS) AF: 0.673 AC: 3464 AN: 5146

South Asian (SAS) AF: 0.473 AC: 2276 AN: 4812

European-Finnish (FIN) AF: 0.582 AC: 6150 AN: 10564

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42372 AN: 67936

Other (OTH) AF: 0.553 AC: 1160 AN: 2098

Alfa AF: 0.574 Hom.: 3123

Bravo AF: 0.525

Asia WGS AF: 0.555 AC: 1932 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 29, 2018

GeneDx

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	-0.85
CADD	Benign	3.2
DANN	Benign	0.86
PhyloP100		0.86
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: rs12876517; hg19: chr13-111009643; COSMIC: COSV64634625;