13-110465726-C-T

Variant names:

• chr13-110465726-C-T
• rs72657953
• NM_001846.4:c.1978+120C>T

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+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 1,005,098 control chromosomes in the GnomAD database, including 3,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (582 hom., cov: 34)
  • Exomes 𝑓: 0.081 (2953 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.35
• Publications: 1 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=-0.89).
• BP6: Variant 13-110465726-C-T is Benign according to our data. Variant chr13-110465726-C-T is described in ClinVar as Benign. ClinVar VariationId is 1246921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1978+120C>T		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.1978+120C>T		intron_variant	Intron 25 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.0842 AC: 12818 AN: 152178 Hom.: 582 Cov.: 34

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0917

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0987

GnomAD4 exome AF: 0.0807 AC: 68791 AN: 852802 Hom.: 2953 AF XY: 0.0812 AC XY: 34826 AN XY: 428986

African (AFR) AF: 0.0914 AC: 1799 AN: 19676

American (AMR) AF: 0.101 AC: 2003 AN: 19926

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 1983 AN: 16290

East Asian (EAS) AF: 0.0746 AC: 2462 AN: 33014

South Asian (SAS) AF: 0.0951 AC: 5144 AN: 54088

European-Finnish (FIN) AF: 0.0645 AC: 2764 AN: 42866

Middle Eastern (MID) AF: 0.153 AC: 426 AN: 2790

European-Non Finnish (NFE) AF: 0.0779 AC: 48666 AN: 624996

Other (OTH) AF: 0.0905 AC: 3544 AN: 39156

GnomAD4 genome AF: 0.0842 AC: 12817 AN: 152296 Hom.: 582 Cov.: 34 AF XY: 0.0844 AC XY: 6284 AN XY: 74470

African (AFR) AF: 0.0878 AC: 3649 AN: 41562

American (AMR) AF: 0.0915 AC: 1400 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3472

East Asian (EAS) AF: 0.104 AC: 536 AN: 5178

South Asian (SAS) AF: 0.0876 AC: 423 AN: 4828

European-Finnish (FIN) AF: 0.0682 AC: 724 AN: 10616

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.0796 AC: 5415 AN: 68024

Other (OTH) AF: 0.0972 AC: 205 AN: 2110

Alfa AF: 0.0812 Hom.: 60

Bravo AF: 0.0893

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.89
CADD	Benign	0.38
DANN	Benign	0.56
PhyloP100		-2.4
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: rs72657953; hg19: chr13-111118073;