Variant 2-206766701-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001136193.2(FASTKD2):c.8C>A(p.Thr3Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FASTKD2
NM_001136193.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0350

Variant links:

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]

FASTKD2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09828785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FASTKD2	NM_001136193.2 linkuse as main transcript	c.8C>A	p.Thr3Lys	missense_variant	2/12	ENST00000402774.8	NP_001129665.1
FASTKD2	NM_001136194.2 linkuse as main transcript	c.8C>A	p.Thr3Lys	missense_variant	2/12		NP_001129666.1
FASTKD2	NM_014929.4 linkuse as main transcript	c.8C>A	p.Thr3Lys	missense_variant	2/12		NP_055744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASTKD2	ENST00000402774.8 linkuse as main transcript	c.8C>A	p.Thr3Lys	missense_variant	2/12	1	NM_001136193.2	ENSP00000385990	P1	Q9NYY8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 3 of the FASTKD2 protein (p.Thr3Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FASTKD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1943390). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.00096

T;T;T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.37

.;T;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.098

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;.;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.53

N;N;N;N

REVEL

Benign

0.046

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.60

P;.;P;P

Vest4

0.12

MutPred

0.21

Gain of MoRF binding (P = 0.0178);Gain of MoRF binding (P = 0.0178);Gain of MoRF binding (P = 0.0178);Gain of MoRF binding (P = 0.0178);

MVP

0.41

MPC

0.21

ClinPred

0.47

GERP RS

2.4

Varity_R

0.15

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over