chr13-110493432-C-T

Variant names:

• chr13-110493432-C-T
• rs9559826
• NM_001846.4:c.3634+150C>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.3634+150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 735,544 control chromosomes in the GnomAD database, including 3,739 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (770 hom., cov: 32)
  • Exomes 𝑓: 0.097 (2969 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.84
• Publications: 3 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=-0.92).
• BP6: Variant 13-110493432-C-T is Benign according to our data. Variant chr13-110493432-C-T is described in ClinVar as Benign. ClinVar VariationId is 1223587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.3634+150C>T		intron	N/A	NP_001837.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.3634+150C>T		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.3715+150C>T		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.3634+150C>T		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15226 AN: 152116 Hom.: 768 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.0934

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0847

GnomAD4 exome AF: 0.0967 AC: 56434 AN: 583310 Hom.: 2969 AF XY: 0.0956 AC XY: 29262 AN XY: 306030

African (AFR) AF: 0.0925 AC: 1386 AN: 14976

American (AMR) AF: 0.106 AC: 2283 AN: 21468

Ashkenazi Jewish (ASJ) AF: 0.0561 AC: 890 AN: 15874

East Asian (EAS) AF: 0.128 AC: 4069 AN: 31870

South Asian (SAS) AF: 0.0698 AC: 3647 AN: 52226

European-Finnish (FIN) AF: 0.0789 AC: 2630 AN: 33324

Middle Eastern (MID) AF: 0.0531 AC: 154 AN: 2902

European-Non Finnish (NFE) AF: 0.101 AC: 38470 AN: 379920

Other (OTH) AF: 0.0945 AC: 2905 AN: 30750

GnomAD4 genome AF: 0.100 AC: 15244 AN: 152234 Hom.: 770 Cov.: 32 AF XY: 0.0996 AC XY: 7418 AN XY: 74442

African (AFR) AF: 0.0970 AC: 4030 AN: 41548

American (AMR) AF: 0.0932 AC: 1425 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 214 AN: 3472

East Asian (EAS) AF: 0.168 AC: 870 AN: 5176

South Asian (SAS) AF: 0.0743 AC: 358 AN: 4820

European-Finnish (FIN) AF: 0.0723 AC: 768 AN: 10616

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7214 AN: 67998

Other (OTH) AF: 0.0852 AC: 180 AN: 2112

Alfa AF: 0.104 Hom.: 535

Bravo AF: 0.103

Asia WGS AF: 0.107 AC: 372 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.77
PhyloP100		-3.8
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: rs9559826; hg19: chr13-111145779; COSMIC: COSV107471776;