chr3-30644932-A-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003242.6(TGFBR2):c.263+17A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,611,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_003242.6 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGFBR2 | ENST00000295754.10 | c.263+17A>C | intron_variant | Intron 2 of 6 | 1 | NM_003242.6 | ENSP00000295754.5 | |||
TGFBR2 | ENST00000359013.4 | c.338+17A>C | intron_variant | Intron 3 of 7 | 1 | ENSP00000351905.4 | ||||
TGFBR2 | ENST00000672866.1 | n.1859+17A>C | intron_variant | Intron 2 of 6 | ||||||
TGFBR2 | ENST00000673250.1 | n.387+17A>C | intron_variant | Intron 3 of 3 |
Frequencies
GnomAD3 genomes AF: 0.000283 AC: 43AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000168 AC: 42AN: 250736Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135538
GnomAD4 exome AF: 0.000217 AC: 317AN: 1458798Hom.: 0 Cov.: 31 AF XY: 0.000197 AC XY: 143AN XY: 726014
GnomAD4 genome AF: 0.000282 AC: 43AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74406
ClinVar
Submissions by phenotype
not specified Benign:2
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. -
Variant summary: TGFBR2 c.263+17A>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00017 in 250832 control chromosomes. The observed variant frequency is approximately 55- fold the estimated maximal expected allele frequency for a pathogenic variant in TGFBR2 causing Loeys-Dietz Syndrome phenotype (3.1e-06), strongly suggesting that the variant is benign. c.263+17A>C has been reported in the literature an individual affected with breast cancer (Barlow_2003). This report does not provide unequivocal conclusions about association of the variant with Loeys-Dietz Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One other clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign. -
Malignant tumor of esophagus;C1860896:Colorectal cancer, hereditary nonpolyposis, type 6;C2674574:Loeys-Dietz syndrome 2 Benign:1
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Familial thoracic aortic aneurysm and aortic dissection Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at