rs10509

Variant names:

• chr13-110512608-C-A
• rs10509
• NM_001846.4:c.*417C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110512608-C-A
• chr13-110512608-C-G
• chr13-110512608-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001846.4(COL4A2):​c.*417C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL4A2 NM_001846.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.07
• Publications: 10 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

ENSG00000289010 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.*417C>A		3_prime_UTR_variant	Exon 48 of 48	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.*417C>A		3_prime_UTR_variant	Exon 48 of 48	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 28152 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14336

African (AFR) AF: 0.00 AC: 0 AN: 522

American (AMR) AF: 0.00 AC: 0 AN: 1436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 766

East Asian (EAS) AF: 0.00 AC: 0 AN: 610

South Asian (SAS) AF: 0.00 AC: 0 AN: 2660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 18988

Other (OTH) AF: 0.00 AC: 0 AN: 1778

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 2972

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.28
PhyloP100		-4.1

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: rs10509; hg19: chr13-111164955;