chr14-24240639-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001099274.3(TINF2):c.841G>A(p.Glu281Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000083 in 1,614,188 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001099274.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000513 AC: 78AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000108 AC: 27AN: 249552Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135392
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 727246
GnomAD4 genome AF: 0.000519 AC: 79AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.000578 AC XY: 43AN XY: 74456
ClinVar
Submissions by phenotype
Dyskeratosis congenita Uncertain:1Benign:1
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The p.E281K variant (also known as c.841G>A), located in coding exon 6 of the TINF2 gene, results from a G to A substitution at nucleotide position 841. The glutamic acid at codon 281 is replaced by lysine, an amino acid with similar properties. This variant has been reported in one individual with aplastic anemia, leukocytopenia, and normal telomere length (Walne AJ, Blood 2008 Nov; 112(9):3594-600; Vulliamy T, Clin. Genet. 2012 Jan; 81(1):76-81). This variant was previously reported in the SNPDatabase as rs199422322. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.04% (5/12218) total alleles studied, having been observed in 0.13% (5/3914) African American alleles. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. -
Autosomal recessive congenital ichthyosis 1 Uncertain:1
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not specified Benign:1
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Dyskeratosis congenita, autosomal dominant 3 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Revesz syndrome 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. -
Dyskeratosis congenita, autosomal dominant 1 Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at