2-206766722-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136193.2(FASTKD2):​c.29G>A​(p.Ser10Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S10T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

FASTKD2
NM_001136193.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06347984).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FASTKD2NM_001136193.2 linkuse as main transcriptc.29G>A p.Ser10Asn missense_variant 2/12 ENST00000402774.8 NP_001129665.1
FASTKD2NM_001136194.2 linkuse as main transcriptc.29G>A p.Ser10Asn missense_variant 2/12 NP_001129666.1
FASTKD2NM_014929.4 linkuse as main transcriptc.29G>A p.Ser10Asn missense_variant 2/12 NP_055744.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FASTKD2ENST00000402774.8 linkuse as main transcriptc.29G>A p.Ser10Asn missense_variant 2/121 NM_001136193.2 ENSP00000385990 P1Q9NYY8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
251280
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461816
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000264
ExAC
AF:
0.0000741
AC:
9

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 04, 2023This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 10 of the FASTKD2 protein (p.Ser10Asn). 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. This variant is present in population databases (rs147727753, gnomAD 0.03%). 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: 2200846). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0022
T;T;T;T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.35
.;T;.;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.063
T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.9
L;.;L;L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.38
N;N;N;N
REVEL
Benign
0.068
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Benign
0.12
T;D;T;T
Polyphen
0.027
B;.;B;B
Vest4
0.14
MutPred
0.22
Loss of phosphorylation at S10 (P = 0.0444);Loss of phosphorylation at S10 (P = 0.0444);Loss of phosphorylation at S10 (P = 0.0444);Loss of phosphorylation at S10 (P = 0.0444);
MVP
0.51
MPC
0.20
ClinPred
0.15
T
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147727753; hg19: chr2-207631446; API