rs9559814

Variant names:

• chr13-110469136-A-G
• rs9559814
• NM_001846.4:c.2096-81A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-110469136-A-G
• chr13-110469136-A-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.2096-81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,492,644 control chromosomes in the GnomAD database, including 265,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (28263 hom., cov: 33)
  • Exomes 𝑓: 0.59 (237085 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.45
• 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=-0.89).
• BP6: Variant 13-110469136-A-G is Benign according to our data. Variant chr13-110469136-A-G is described in ClinVar as Benign. ClinVar VariationId is 1274675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.2096-81A>G		intron_variant	Intron 27 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.2096-81A>G		intron_variant	Intron 27 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91235 AN: 151996 Hom.: 28230 Cov.: 33

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.589 AC: 789142 AN: 1340530 Hom.: 237085 AF XY: 0.585 AC XY: 387239 AN XY: 661568

African (AFR) AF: 0.712 AC: 21536 AN: 30258

American (AMR) AF: 0.425 AC: 14838 AN: 34946

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 15877 AN: 24074

East Asian (EAS) AF: 0.250 AC: 8809 AN: 35236

South Asian (SAS) AF: 0.478 AC: 36615 AN: 76646

European-Finnish (FIN) AF: 0.478 AC: 23234 AN: 48594

Middle Eastern (MID) AF: 0.678 AC: 3761 AN: 5544

European-Non Finnish (NFE) AF: 0.614 AC: 631657 AN: 1029438

Other (OTH) AF: 0.588 AC: 32815 AN: 55794

GnomAD4 genome AF: 0.600 AC: 91326 AN: 152114 Hom.: 28263 Cov.: 33 AF XY: 0.588 AC XY: 43742 AN XY: 74352

African (AFR) AF: 0.699 AC: 29005 AN: 41506

American (AMR) AF: 0.500 AC: 7646 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2355 AN: 3468

East Asian (EAS) AF: 0.289 AC: 1497 AN: 5178

South Asian (SAS) AF: 0.457 AC: 2205 AN: 4820

European-Finnish (FIN) AF: 0.465 AC: 4903 AN: 10554

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41606 AN: 67984

Other (OTH) AF: 0.606 AC: 1282 AN: 2116

Alfa AF: 0.534 Hom.: 2723

Bravo AF: 0.607

Asia WGS AF: 0.401 AC: 1396 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	0.026
DANN	Benign	0.47
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: rs9559814; hg19: chr13-111121483; COSMIC: COSV64629152; COSMIC: COSV64629152;