chr13-110450518-G-T

Variant names:

• chr13-110450518-G-T
• rs72657934
• NM_001846.4:c.1339+64G>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.1339+64G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,423,586 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 0 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: 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=-0.88).

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.1339+64G>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.1339+64G>T		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.1420+64G>T		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.1339+64G>T		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1423586 Hom.: 0 AF XY: 0.00000141 AC XY: 1 AN XY: 706950

African (AFR) AF: 0.00 AC: 0 AN: 32574

American (AMR) AF: 0.0000470 AC: 2 AN: 42514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25328

East Asian (EAS) AF: 0.00 AC: 0 AN: 39210

South Asian (SAS) AF: 0.00 AC: 0 AN: 84894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1086714

Other (OTH) AF: 0.00 AC: 0 AN: 58864

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.47
PhyloP100		-0.51

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: rs72657934; hg19: chr13-111102865;