3-30672127-C-T
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2
The NM_003242.6(TGFBR2):c.944C>T(p.Thr315Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 1,614,120 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_003242.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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TGFBR2 | ENST00000295754.10 | c.944C>T | p.Thr315Met | missense_variant | Exon 4 of 7 | 1 | NM_003242.6 | ENSP00000295754.5 | ||
TGFBR2 | ENST00000359013.4 | c.1019C>T | p.Thr340Met | missense_variant | Exon 5 of 8 | 1 | ENSP00000351905.4 | |||
TGFBR2 | ENST00000672866.1 | n.2540C>T | non_coding_transcript_exon_variant | Exon 4 of 7 |
Frequencies
GnomAD3 genomes AF: 0.000493 AC: 75AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00112 AC: 280AN: 251058Hom.: 3 AF XY: 0.00108 AC XY: 146AN XY: 135674
GnomAD4 exome AF: 0.000395 AC: 578AN: 1461858Hom.: 9 Cov.: 34 AF XY: 0.000418 AC XY: 304AN XY: 727228
GnomAD4 genome AF: 0.000486 AC: 74AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37AN XY: 74442
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:4
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This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
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not provided Benign:4
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This variant is associated with the following publications: (PMID: 17935258, 9590282, 22995991, 20144264, 15235604, 16251899, 18339844, 27647783, 31769227) -
TGFBR2: BP4, BS1, BS2 -
Marfan syndrome Benign:2
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not specified Benign:2
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Colorectal cancer, hereditary nonpolyposis, type 6 Pathogenic:1
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Familial colorectal cancer Benign:1
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Loeys-Dietz syndrome Benign:1
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Ehlers-Danlos syndrome Benign:1
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Loeys-Dietz syndrome 2 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at