13-110466949-A-G

Variant names:

• chr13-110466949-A-G
• rs3803232
• NM_001846.4:c.2039-91A>G

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.2039-91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,537,950 control chromosomes in the GnomAD database, including 264,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27910 hom., cov: 32)
  • Exomes 𝑓: 0.58 (236628 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.625
• Publications: 9 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=-0.91).
• BP6: Variant 13-110466949-A-G is Benign according to our data. Variant chr13-110466949-A-G is described in ClinVar as Benign. ClinVar VariationId is 1238254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2039-91A>G		intron_variant	Intron 26 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2039-91A>G		intron_variant	Intron 26 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90525 AN: 151982 Hom.: 27874 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.599

GnomAD4 exome AF: 0.578 AC: 800760 AN: 1385850 Hom.: 236628 AF XY: 0.575 AC XY: 396269 AN XY: 688736

African (AFR) AF: 0.722 AC: 22780 AN: 31548

American (AMR) AF: 0.408 AC: 16759 AN: 41100

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 15920 AN: 24468

East Asian (EAS) AF: 0.255 AC: 9739 AN: 38238

South Asian (SAS) AF: 0.477 AC: 38943 AN: 81636

European-Finnish (FIN) AF: 0.444 AC: 23367 AN: 52572

Middle Eastern (MID) AF: 0.670 AC: 3689 AN: 5502

European-Non Finnish (NFE) AF: 0.604 AC: 636286 AN: 1053502

Other (OTH) AF: 0.581 AC: 33277 AN: 57284

GnomAD4 genome AF: 0.596 AC: 90622 AN: 152100 Hom.: 27910 Cov.: 32 AF XY: 0.583 AC XY: 43363 AN XY: 74360

African (AFR) AF: 0.709 AC: 29416 AN: 41502

American (AMR) AF: 0.502 AC: 7668 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2326 AN: 3468

East Asian (EAS) AF: 0.292 AC: 1512 AN: 5170

South Asian (SAS) AF: 0.463 AC: 2232 AN: 4822

European-Finnish (FIN) AF: 0.429 AC: 4534 AN: 10574

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40839 AN: 67954

Other (OTH) AF: 0.598 AC: 1266 AN: 2116

Alfa AF: 0.605 Hom.: 66365

Bravo AF: 0.605

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		-0.63
PromoterAI		-0.0044	Neutral
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: rs3803232; hg19: chr13-111119296;