chr13-110492218-C-T

Variant names:

• chr13-110492218-C-T
• rs421177
• NM_001846.4:c.3562+41C>T

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.3562+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,527,260 control chromosomes in the GnomAD database, including 18,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2627 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15753 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.63
• Publications: 7 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=-0.89).
• BP6: Variant 13-110492218-C-T is Benign according to our data. Variant chr13-110492218-C-T is described in ClinVar as [Benign]. Clinvar id is 1178451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.3562+41C>T		intron_variant	Intron 38 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.3562+41C>T		intron_variant	Intron 38 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27057 AN: 152060 Hom.: 2623 Cov.: 33

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.169

GnomAD2 exomes AF: 0.167 AC: 25321 AN: 151842 AF XY: 0.171

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.0978

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.145 AC: 199020 AN: 1375082 Hom.: 15753 Cov.: 24 AF XY: 0.147 AC XY: 99893 AN XY: 679702

African (AFR) AF: 0.249 AC: 7729 AN: 31098

American (AMR) AF: 0.103 AC: 3666 AN: 35578

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 4865 AN: 24988

East Asian (EAS) AF: 0.188 AC: 6687 AN: 35562

South Asian (SAS) AF: 0.228 AC: 17879 AN: 78512

European-Finnish (FIN) AF: 0.259 AC: 12721 AN: 49146

Middle Eastern (MID) AF: 0.173 AC: 980 AN: 5652

European-Non Finnish (NFE) AF: 0.128 AC: 135503 AN: 1057450

Other (OTH) AF: 0.157 AC: 8990 AN: 57096

GnomAD4 genome AF: 0.178 AC: 27089 AN: 152178 Hom.: 2627 Cov.: 33 AF XY: 0.183 AC XY: 13607 AN XY: 74386

African (AFR) AF: 0.241 AC: 9988 AN: 41528

American (AMR) AF: 0.138 AC: 2107 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3470

East Asian (EAS) AF: 0.171 AC: 885 AN: 5168

South Asian (SAS) AF: 0.246 AC: 1189 AN: 4824

European-Finnish (FIN) AF: 0.260 AC: 2750 AN: 10584

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9032 AN: 67994

Other (OTH) AF: 0.169 AC: 356 AN: 2112

Alfa AF: 0.164 Hom.: 439

Bravo AF: 0.168

Asia WGS AF: 0.182 AC: 630 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

- -

Jul 05, 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	-0.89
CADD	Benign	0.62
DANN	Benign	0.65
PhyloP100		-1.6
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: rs421177; hg19: chr13-111144565; COSMIC: COSV64633821;