rs10509

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-110512608-C-G
• chr13-110512608-C-A
• chr13-110512608-C-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.*417C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 180,346 control chromosomes in the GnomAD database, including 70,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (58859 hom., cov: 33)
  • Exomes 𝑓: 0.91 (11661 hom.)
• Consequence: COL4A2 NM_001846.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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), G2P, Ambry Genetics
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 13-110512608-C-G is Benign according to our data. Variant chr13-110512608-C-G is described in ClinVar as Benign. ClinVar VariationId is 311205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.*417C>G		3_prime_UTR	Exon 48 of 48	NP_001837.2	P08572

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.*417C>G		3_prime_UTR	Exon 48 of 48	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.*417C>G		3_prime_UTR	Exon 49 of 49	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.*417C>G		3_prime_UTR	Exon 48 of 48	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133482 AN: 152116 Hom.: 58820 Cov.: 33

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.860

GnomAD4 exome AF: 0.910 AC: 25587 AN: 28112 Hom.: 11661 Cov.: 0 AF XY: 0.913 AC XY: 13064 AN XY: 14314

African (AFR) AF: 0.785 AC: 408 AN: 520

American (AMR) AF: 0.896 AC: 1281 AN: 1430

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 637 AN: 766

East Asian (EAS) AF: 0.933 AC: 569 AN: 610

South Asian (SAS) AF: 0.935 AC: 2484 AN: 2658

European-Finnish (FIN) AF: 0.947 AC: 1203 AN: 1270

Middle Eastern (MID) AF: 0.858 AC: 103 AN: 120

European-Non Finnish (NFE) AF: 0.913 AC: 17315 AN: 18964

Other (OTH) AF: 0.895 AC: 1587 AN: 1774

GnomAD4 genome AF: 0.877 AC: 133581 AN: 152234 Hom.: 58859 Cov.: 33 AF XY: 0.883 AC XY: 65695 AN XY: 74438

African (AFR) AF: 0.783 AC: 32479 AN: 41486

American (AMR) AF: 0.889 AC: 13596 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2886 AN: 3472

East Asian (EAS) AF: 0.947 AC: 4901 AN: 5178

South Asian (SAS) AF: 0.953 AC: 4601 AN: 4828

European-Finnish (FIN) AF: 0.954 AC: 10121 AN: 10610

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.912 AC: 62025 AN: 68036

Other (OTH) AF: 0.861 AC: 1821 AN: 2116

Alfa AF: 0.894 Hom.: 2972

Bravo AF: 0.867

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Porencephaly 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.48
PhyloP100		-4.1
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10509;

hg19: chr13-111164955;