1-27881973-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001105556.3(THEMIS2):c.649C>T(p.Arg217Cys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000106 in 1,608,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R217H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001105556.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000123 AC: 3AN: 242930Hom.: 0 AF XY: 0.0000228 AC XY: 3AN XY: 131830
GnomAD4 exome AF: 0.00000961 AC: 14AN: 1456488Hom.: 0 Cov.: 30 AF XY: 0.00000967 AC XY: 7AN XY: 724178
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.649C>T (p.R217C) alteration is located in exon 4 (coding exon 4) of the THEMIS2 gene. This alteration results from a C to T substitution at nucleotide position 649, causing the arginine (R) at amino acid position 217 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at