rs2296853
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001846.4(COL4A2):c.2903-12A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,601,718 control chromosomes in the GnomAD database, including 22,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.14 ( 1872 hom., cov: 31)
Exomes 𝑓: 0.16 ( 20418 hom. )
Consequence
COL4A2
NM_001846.4 splice_polypyrimidine_tract, intron
NM_001846.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00002152
2
Clinical Significance
Conservation
PhyloP100: -0.147
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 13-110484893-A-G is Benign according to our data. Variant chr13-110484893-A-G is described in ClinVar as [Benign]. Clinvar id is 311153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-110484893-A-G is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A2 | NM_001846.4 | c.2903-12A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000360467.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A2 | ENST00000360467.7 | c.2903-12A>G | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001846.4 | P1 | |||
COL4A2 | ENST00000650225.1 | n.558-12A>G | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.140 AC: 21181AN: 151796Hom.: 1868 Cov.: 31
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GnomAD3 exomes AF: 0.159 AC: 38469AN: 242686Hom.: 3414 AF XY: 0.156 AC XY: 20523AN XY: 131956
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GnomAD4 exome AF: 0.163 AC: 236686AN: 1449800Hom.: 20418 Cov.: 33 AF XY: 0.161 AC XY: 116103AN XY: 720514
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GnomAD4 genome ? AF: 0.139 AC: 21188AN: 151918Hom.: 1872 Cov.: 31 AF XY: 0.141 AC XY: 10468AN XY: 74264
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 02, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Porencephaly 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at