chr2-206766737-G-A

Position:

chr2-206766737-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001136193.2(FASTKD2):c.44G>A(p.Ser15Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 1,613,708 control chromosomes in the GnomAD database, including 7,451 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S15G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.12 ( 1539 hom., cov: 33)

Exomes 𝑓: 0.083 ( 5912 hom. )

Consequence

FASTKD2
NM_001136193.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0400

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004671097).

BP6

Variant 2-206766737-G-A is Benign according to our data. Variant chr2-206766737-G-A is described in ClinVar as [Benign]. Clinvar id is 333800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-206766737-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FASTKD2	NM_001136193.2 linkuse as main transcript	c.44G>A	p.Ser15Asn	missense_variant	2/12	ENST00000402774.8
FASTKD2	NM_001136194.2 linkuse as main transcript	c.44G>A	p.Ser15Asn	missense_variant	2/12
FASTKD2	NM_014929.4 linkuse as main transcript	c.44G>A	p.Ser15Asn	missense_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASTKD2	ENST00000402774.8 linkuse as main transcript	c.44G>A	p.Ser15Asn	missense_variant	2/12	1	NM_001136193.2	P1	Q9NYY8-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18123

AN:

152078

Hom.:

1528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0761

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.0470

Gnomad SAS

AF:

0.0877

Gnomad FIN

AF:

0.0509

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0775

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.0795

AC:

19976

AN:

251196

Hom.:

1140

AF XY:

0.0783

AC XY:

10635

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.253

Gnomad AMR exome

AF:

0.0466

Gnomad ASJ exome

AF:

0.0412

Gnomad EAS exome

AF:

0.0401

Gnomad SAS exome

AF:

0.0882

Gnomad FIN exome

AF:

0.0551

Gnomad NFE exome

AF:

0.0771

Gnomad OTH exome

AF:

0.0761

GnomAD4 exome

AF:

0.0832

AC:

121647

AN:

1461510

Hom.:

5912

Cov.:

AF XY:

0.0825

AC XY:

59991

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.0507

Gnomad4 ASJ exome

AF:

0.0417

Gnomad4 EAS exome

AF:

0.0433

Gnomad4 SAS exome

AF:

0.0901

Gnomad4 FIN exome

AF:

0.0578

Gnomad4 NFE exome

AF:

0.0824

Gnomad4 OTH exome

AF:

0.0880

GnomAD4 genome

AF:

0.119

AC:

18171

AN:

152198

Hom.:

1539

Cov.:

AF XY:

0.116

AC XY:

8665

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.0758

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.0468

Gnomad4 SAS

AF:

0.0880

Gnomad4 FIN

AF:

0.0509

Gnomad4 NFE

AF:

0.0775

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.0891

Hom.:

868

Bravo

AF:

0.126

TwinsUK

AF:

0.0844

AC:

313

ALSPAC

AF:

0.0737

AC:

284

ESP6500AA

AF:

0.244

AC:

1075

ESP6500EA

AF:

0.0758

AC:

652

ExAC

AF:

0.0842

AC:

10217

Asia WGS

AF:

0.0830

AC:

289

AN:

3478

EpiCase

AF:

0.0788

EpiControl

AF:

0.0798

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 15, 2016	- -

Mitochondrial complex IV deficiency, nuclear type 1

Benign:1

Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.5

DANN

Benign

0.97

DEOGEN2

Benign

0.0037

T;T;T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.35

.;T;.;T

MetaRNN

Benign

0.0047

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.;L;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.37

N;N;N;N

REVEL

Benign

0.084

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.031

D;D;D;D

Polyphen

0.0050

B;.;B;B

Vest4

0.018

MPC

0.15

ClinPred

0.011

GERP RS

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over