rs7334986

Variant names:

• chr13-110428262-G-A
• rs7334986
• NM_001846.4:c.361-205G>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.361-205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,080 control chromosomes in the GnomAD database, including 6,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.29 (6644 hom., cov: 33)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.112
• 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=-0.89).
• BP6: Variant 13-110428262-G-A is Benign according to our data. Variant chr13-110428262-G-A is described in ClinVar as Benign. ClinVar VariationId is 1262336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.361-205G>A		intron_variant	Intron 6 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.361-205G>A		intron_variant	Intron 6 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43327 AN: 151962 Hom.: 6630 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.298

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.285 AC: 43386 AN: 152080 Hom.: 6644 Cov.: 33 AF XY: 0.281 AC XY: 20889 AN XY: 74352

African (AFR) AF: 0.380 AC: 15742 AN: 41446

American (AMR) AF: 0.229 AC: 3504 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3464

East Asian (EAS) AF: 0.156 AC: 808 AN: 5182

South Asian (SAS) AF: 0.265 AC: 1281 AN: 4828

European-Finnish (FIN) AF: 0.223 AC: 2360 AN: 10560

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17594 AN: 67992

Other (OTH) AF: 0.301 AC: 635 AN: 2108

Alfa AF: 0.282 Hom.: 945

Bravo AF: 0.291

Asia WGS AF: 0.222 AC: 776 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.51
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7334986; hg19: chr13-111080609;