chr13-110438562-T-C

Variant names:

• chr13-110438562-T-C
• rs7984937
• NM_001846.4:c.862-56T>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.862-56T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,607,394 control chromosomes in the GnomAD database, including 75,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10398 hom., cov: 33)
  • Exomes 𝑓: 0.29 (64642 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.148
• Publications: 5 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 (REVEL=0.004).
• BP6: Variant 13-110438562-T-C is Benign according to our data. Variant chr13-110438562-T-C is described in ClinVar as Benign. ClinVar VariationId is 1272751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.862-56T>C		intron_variant	Intron 14 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.862-56T>C		intron_variant	Intron 14 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53397 AN: 151780 Hom.: 10391 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.353

GnomAD2 exomes AF: 0.284 AC: 70880 AN: 249408 AF XY: 0.282

Gnomad AFR exome AF: 0.543

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.449

Gnomad EAS exome AF: 0.145

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.306

GnomAD4 exome AF: 0.290 AC: 422437 AN: 1455496 Hom.: 64642 Cov.: 30 AF XY: 0.288 AC XY: 208927 AN XY: 724546

African (AFR) AF: 0.540 AC: 18011 AN: 33340

American (AMR) AF: 0.206 AC: 9222 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 11573 AN: 26082

East Asian (EAS) AF: 0.116 AC: 4601 AN: 39658

South Asian (SAS) AF: 0.224 AC: 19264 AN: 86134

European-Finnish (FIN) AF: 0.289 AC: 15406 AN: 53364

Middle Eastern (MID) AF: 0.463 AC: 2663 AN: 5750

European-Non Finnish (NFE) AF: 0.292 AC: 322833 AN: 1106248

Other (OTH) AF: 0.313 AC: 18864 AN: 60208

GnomAD4 genome AF: 0.352 AC: 53440 AN: 151898 Hom.: 10398 Cov.: 33 AF XY: 0.346 AC XY: 25709 AN XY: 74238

African (AFR) AF: 0.531 AC: 21952 AN: 41370

American (AMR) AF: 0.292 AC: 4464 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1486 AN: 3466

East Asian (EAS) AF: 0.127 AC: 657 AN: 5170

South Asian (SAS) AF: 0.207 AC: 998 AN: 4830

European-Finnish (FIN) AF: 0.286 AC: 3018 AN: 10554

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19762 AN: 67918

Other (OTH) AF: 0.354 AC: 748 AN: 2112

Alfa AF: 0.326 Hom.: 4182

Bravo AF: 0.364

Asia WGS AF: 0.211 AC: 733 AN: 3476

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

- -

Jul 09, 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	4.3
DANN	Benign	0.27
PhyloP100		-0.15
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: rs7984937; hg19: chr13-111090909; COSMIC: COSV64631986;