rs1983931

Variant names:

• chr13-110465755-G-A
• rs1983931
• NM_001846.4:c.1978+149G>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.1978+149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 862,410 control chromosomes in the GnomAD database, including 141,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (25158 hom., cov: 33)
  • Exomes 𝑓: 0.56 (116273 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.665
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 13-110465755-G-A is Benign according to our data. Variant chr13-110465755-G-A is described in ClinVar as Benign. ClinVar VariationId is 1238517.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.1978+149G>A		intron	N/A	NP_001837.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.1978+149G>A		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.2059+149G>A		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.1978+149G>A		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86297 AN: 151978 Hom.: 25142 Cov.: 33

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.562 AC: 399152 AN: 710314 Hom.: 116273 AF XY: 0.560 AC XY: 201854 AN XY: 360748

African (AFR) AF: 0.618 AC: 10525 AN: 17028

American (AMR) AF: 0.445 AC: 8215 AN: 18452

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 9893 AN: 15308

East Asian (EAS) AF: 0.242 AC: 7791 AN: 32214

South Asian (SAS) AF: 0.472 AC: 23588 AN: 49958

European-Finnish (FIN) AF: 0.442 AC: 17557 AN: 39736

Middle Eastern (MID) AF: 0.641 AC: 1588 AN: 2476

European-Non Finnish (NFE) AF: 0.600 AC: 300390 AN: 500726

Other (OTH) AF: 0.570 AC: 19605 AN: 34416

GnomAD4 genome AF: 0.568 AC: 86368 AN: 152096 Hom.: 25158 Cov.: 33 AF XY: 0.556 AC XY: 41342 AN XY: 74352

African (AFR) AF: 0.615 AC: 25496 AN: 41478

American (AMR) AF: 0.494 AC: 7551 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2316 AN: 3468

East Asian (EAS) AF: 0.282 AC: 1456 AN: 5172

South Asian (SAS) AF: 0.460 AC: 2221 AN: 4828

European-Finnish (FIN) AF: 0.429 AC: 4535 AN: 10576

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40737 AN: 67960

Other (OTH) AF: 0.581 AC: 1229 AN: 2116

Alfa AF: 0.595 Hom.: 38823

Bravo AF: 0.574

Asia WGS AF: 0.392 AC: 1364 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-0.67
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: rs1983931; hg19: chr13-111118102;