rs1983932

Variant names:

• chr13-110465874-T-C
• rs1983932
• NM_001846.4:c.1979-129T>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.1979-129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 1,182,920 control chromosomes in the GnomAD database, including 201,744 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26306 hom., cov: 32)
  • Exomes 𝑓: 0.58 (175438 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.22
• Publications: 2 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 13-110465874-T-C is Benign according to our data. Variant chr13-110465874-T-C is described in ClinVar as Benign. ClinVar VariationId is 1293747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1979-129T>C		intron_variant	Intron 25 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1979-129T>C		intron_variant	Intron 25 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88178 AN: 151926 Hom.: 26282 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.591

GnomAD4 exome AF: 0.576 AC: 593892 AN: 1030876 Hom.: 175438 AF XY: 0.574 AC XY: 295428 AN XY: 515074

African (AFR) AF: 0.665 AC: 15759 AN: 23696

American (AMR) AF: 0.429 AC: 11134 AN: 25944

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 11595 AN: 17824

East Asian (EAS) AF: 0.256 AC: 9352 AN: 36510

South Asian (SAS) AF: 0.476 AC: 28219 AN: 59272

European-Finnish (FIN) AF: 0.447 AC: 21827 AN: 48810

Middle Eastern (MID) AF: 0.664 AC: 2568 AN: 3868

European-Non Finnish (NFE) AF: 0.607 AC: 467471 AN: 769980

Other (OTH) AF: 0.577 AC: 25967 AN: 44972

GnomAD4 genome AF: 0.580 AC: 88259 AN: 152044 Hom.: 26306 Cov.: 32 AF XY: 0.568 AC XY: 42224 AN XY: 74336

African (AFR) AF: 0.653 AC: 27089 AN: 41458

American (AMR) AF: 0.499 AC: 7621 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2328 AN: 3472

East Asian (EAS) AF: 0.293 AC: 1512 AN: 5162

South Asian (SAS) AF: 0.462 AC: 2217 AN: 4802

European-Finnish (FIN) AF: 0.430 AC: 4556 AN: 10590

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

European-Non Finnish (NFE) AF: 0.601 AC: 40860 AN: 67962

Other (OTH) AF: 0.590 AC: 1247 AN: 2112

Alfa AF: 0.601 Hom.: 3586

Bravo AF: 0.588

Asia WGS AF: 0.400 AC: 1393 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	0.18
DANN	Benign	0.21
PhyloP100		-2.2
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: rs1983932; hg19: chr13-111118221; COSMIC: COSV64632519; COSMIC: COSV64632519;