chr10-112950840-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001367943.1(TCF7L2):āc.84G>Cā(p.Glu28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,608,322 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 (ā ).
Frequency
Consequence
NM_001367943.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TCF7L2 | NM_001367943.1 | c.84G>C | p.Glu28Asp | missense_variant | Exon 1 of 15 | ENST00000355995.9 | NP_001354872.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152112Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.0000413 AC: 10AN: 242200Hom.: 0 AF XY: 0.0000459 AC XY: 6AN XY: 130828
GnomAD4 exome AF: 0.000149 AC: 217AN: 1456210Hom.: 0 Cov.: 32 AF XY: 0.000115 AC XY: 83AN XY: 723818
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152112Hom.: 0 Cov.: 29 AF XY: 0.0000538 AC XY: 4AN XY: 74302
ClinVar
Submissions by phenotype
not provided Uncertain:1
The TCF7L2 p.E28D variant was not identified in the literature nor was it identified in ClinVar, Cosmic, or LOVD 3.0. The variant was identified in dbSNP (ID: rs373425129) and in control databases in 10 of 242200 chromosomes at a frequency of 0.000041 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European (non-Finnish) population in 10 of 109400 chromosomes (freq: 0.000091), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other or South Asian populations. The p.Glu28 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Inborn genetic diseases Benign:1
This alteration is classified as likely 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at