rs9559818

Variant names:

• chr13-110477879-G-A
• rs9559818
• NM_001846.4:c.2426-124G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110477879-G-A
• chr13-110477879-G-C

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.2426-124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 986,188 control chromosomes in the GnomAD database, including 100,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (13995 hom., cov: 33)
  • Exomes 𝑓: 0.45 (86130 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.243
• Publications: 6 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=-0.81).
• BP6: Variant 13-110477879-G-A is Benign according to our data. Variant chr13-110477879-G-A is described in ClinVar as Benign. ClinVar VariationId is 1260163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2426-124G>A		intron_variant	Intron 29 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2426-124G>A		intron_variant	Intron 29 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64880 AN: 151950 Hom.: 13984 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.453 AC: 378135 AN: 834122 Hom.: 86130 Cov.: 11 AF XY: 0.455 AC XY: 185207 AN XY: 407112

African (AFR) AF: 0.372 AC: 6850 AN: 18438

American (AMR) AF: 0.419 AC: 5601 AN: 13362

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 6384 AN: 13138

East Asian (EAS) AF: 0.407 AC: 11406 AN: 28020

South Asian (SAS) AF: 0.465 AC: 9640 AN: 20712

European-Finnish (FIN) AF: 0.423 AC: 16497 AN: 38956

Middle Eastern (MID) AF: 0.523 AC: 2098 AN: 4014

European-Non Finnish (NFE) AF: 0.458 AC: 303234 AN: 661744

Other (OTH) AF: 0.460 AC: 16425 AN: 35738

GnomAD4 genome AF: 0.427 AC: 64929 AN: 152066 Hom.: 13995 Cov.: 33 AF XY: 0.426 AC XY: 31689 AN XY: 74340

African (AFR) AF: 0.376 AC: 15606 AN: 41484

American (AMR) AF: 0.422 AC: 6456 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1701 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2232 AN: 5156

South Asian (SAS) AF: 0.462 AC: 2223 AN: 4812

European-Finnish (FIN) AF: 0.423 AC: 4473 AN: 10574

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30784 AN: 67966

Other (OTH) AF: 0.457 AC: 964 AN: 2110

Alfa AF: 0.433 Hom.: 2289

Bravo AF: 0.425

Asia WGS AF: 0.453 AC: 1577 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 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	-0.81
CADD	Benign	7.7
DANN	Benign	0.44
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9559818; hg19: chr13-111130226; COSMIC: COSV107471773; COSMIC: COSV107471773;