2-206765369-C-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000236980.10(FASTKD2):c.-336C>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 0.087 in 1,505,988 control chromosomes in the GnomAD database, including 6,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.12 ( 1492 hom., cov: 32)
Exomes 𝑓: 0.084 ( 5416 hom. )
Consequence
FASTKD2
ENST00000236980.10 5_prime_UTR
ENST00000236980.10 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.851
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]
MDH1B (HGNC:17836): (malate dehydrogenase 1B) Predicted to enable L-malate dehydrogenase activity. Predicted to be involved in NADH metabolic process; dicarboxylic acid metabolic process; and tricarboxylic acid cycle. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 2-206765369-C-A is Benign according to our data. Variant chr2-206765369-C-A is described in ClinVar as [Benign]. Clinvar id is 1253085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MDH1B | NM_001039845.3 | upstream_gene_variant | ENST00000374412.8 | NP_001034934.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FASTKD2 | ENST00000236980.10 | c.-336C>A | 5_prime_UTR_variant | 1/12 | 1 | ENSP00000236980 | P1 | |||
FASTKD2 | ENST00000418289.1 | c.-200C>A | 5_prime_UTR_variant | 1/2 | 3 | ENSP00000409927 | ||||
MDH1B | ENST00000374412.8 | upstream_gene_variant | 1 | NM_001039845.3 | ENSP00000363533 | P4 | ||||
MDH1B | ENST00000449792.5 | upstream_gene_variant | 5 | ENSP00000416577 |
Frequencies
GnomAD3 genomes AF: 0.118 AC: 17915AN: 152066Hom.: 1485 Cov.: 32
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GnomAD4 exome AF: 0.0835 AC: 113100AN: 1353804Hom.: 5416 Cov.: 31 AF XY: 0.0830 AC XY: 55274AN XY: 665778
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GnomAD4 genome AF: 0.118 AC: 17949AN: 152184Hom.: 1492 Cov.: 32 AF XY: 0.115 AC XY: 8549AN XY: 74400
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 16, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at