rs2296852

Variant names:

• chr13-110485118-G-A
• rs2296852
• NM_001846.4:c.3025+91G>A

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.3025+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,180,764 control chromosomes in the GnomAD database, including 10,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1133 hom., cov: 31)
  • Exomes 𝑓: 0.13 (9230 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.784
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), 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=-0.94).
• BP6: Variant 13-110485118-G-A is Benign according to our data. Variant chr13-110485118-G-A is described in ClinVar as Benign. ClinVar VariationId is 1275084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.3025+91G>A		intron	N/A	NP_001837.2	P08572

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.3025+91G>A		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.3106+91G>A		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.3025+91G>A		intron	N/A	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18870 AN: 152012 Hom.: 1133 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.132 AC: 135594 AN: 1028632 Hom.: 9230 AF XY: 0.131 AC XY: 66095 AN XY: 503762

African (AFR) AF: 0.119 AC: 2807 AN: 23618

American (AMR) AF: 0.118 AC: 2350 AN: 19888

Ashkenazi Jewish (ASJ) AF: 0.0960 AC: 1577 AN: 16430

East Asian (EAS) AF: 0.120 AC: 3960 AN: 33096

South Asian (SAS) AF: 0.115 AC: 5624 AN: 49056

European-Finnish (FIN) AF: 0.117 AC: 4866 AN: 41422

Middle Eastern (MID) AF: 0.0934 AC: 316 AN: 3384

European-Non Finnish (NFE) AF: 0.136 AC: 108612 AN: 798000

Other (OTH) AF: 0.125 AC: 5482 AN: 43738

GnomAD4 genome AF: 0.124 AC: 18894 AN: 152132 Hom.: 1133 Cov.: 31 AF XY: 0.124 AC XY: 9244 AN XY: 74374

African (AFR) AF: 0.120 AC: 4969 AN: 41520

American (AMR) AF: 0.106 AC: 1626 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3472

East Asian (EAS) AF: 0.167 AC: 861 AN: 5158

South Asian (SAS) AF: 0.115 AC: 556 AN: 4816

European-Finnish (FIN) AF: 0.107 AC: 1137 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8924 AN: 67984

Other (OTH) AF: 0.118 AC: 248 AN: 2110

Alfa AF: 0.130 Hom.: 162

Bravo AF: 0.126

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-0.78
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: rs2296852; hg19: chr13-111137465; COSMIC: COSV107471774;