2-206765668-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001136193.2(FASTKD2):c.-130G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000966 in 355,090 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00078 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0011 ( 1 hom. )
Consequence
FASTKD2
NM_001136193.2 5_prime_UTR
NM_001136193.2 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.423
Genes affected
FASTKD2 (HGNC:29160): (FAST kinase domains 2) This gene encodes a protein that is localized in the mitochondrial inner compartment and that may play a role in mitochondrial apoptosis. Nonsense mutations have been reported to result in cytochrome c oxidase deficiency. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 2-206765668-G-A is Benign according to our data. Variant chr2-206765668-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 333796.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FASTKD2 | NM_001136193.2 | c.-130G>A | 5_prime_UTR_variant | 1/12 | ENST00000402774.8 | NP_001129665.1 | ||
FASTKD2 | NM_001136194.2 | c.-145G>A | 5_prime_UTR_variant | 1/12 | NP_001129666.1 | |||
FASTKD2 | NM_014929.4 | c.-51+14G>A | intron_variant | NP_055744.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FASTKD2 | ENST00000402774.8 | c.-130G>A | 5_prime_UTR_variant | 1/12 | 1 | NM_001136193.2 | ENSP00000385990 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000782 AC: 119AN: 152136Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00110 AC: 224AN: 202954Hom.: 1 Cov.: 5 AF XY: 0.00131 AC XY: 127AN XY: 97166
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GnomAD4 genome AF: 0.000782 AC: 119AN: 152136Hom.: 0 Cov.: 31 AF XY: 0.000767 AC XY: 57AN XY: 74298
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Mitochondrial complex IV deficiency, nuclear type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at