13-110465321-G-T

Variant names:

• chr13-110465321-G-T
• rs3803237
• NM_001846.4:c.1777-84G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS2

The NM_001846.4(COL4A2):​c.1777-84G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,330,630 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: 34)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546
• 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 -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A2	NM_001846.4	c.1777-84G>T		intron_variant	Intron 24 of 47	ENST00000360467.7	NP_001837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A2	ENST00000360467.7	c.1777-84G>T		intron_variant	Intron 24 of 47	5	NM_001846.4	ENSP00000353654.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000376 AC: 5 AN: 1330630 Hom.: 0 AF XY: 0.00000306 AC XY: 2 AN XY: 654620

African (AFR) AF: 0.00 AC: 0 AN: 29126

American (AMR) AF: 0.00 AC: 0 AN: 29594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20002

East Asian (EAS) AF: 0.00 AC: 0 AN: 38318

South Asian (SAS) AF: 0.00 AC: 0 AN: 68240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3636

European-Non Finnish (NFE) AF: 0.00000482 AC: 5 AN: 1038374

Other (OTH) AF: 0.00 AC: 0 AN: 54938

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.49
PhyloP100		-0.55

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: rs3803237; hg19: chr13-111117668;