rs79652942

Positions:

chr2-206772253-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001136193.2(FASTKD2):c.1187A>G(p.Asn396Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00185 in 1,613,872 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 13 hom. )

Consequence

FASTKD2
NM_001136193.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.74

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=0.004810989).

BP6

Variant 2-206772253-A-G is Benign according to our data. Variant chr2-206772253-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 214348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00979 (1492/152356) while in subpopulation AFR AF= 0.0328 (1364/41578). AF 95% confidence interval is 0.0314. There are 26 homozygotes in gnomad4. There are 697 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FASTKD2	NM_001136193.2 linkuse as main transcript	c.1187A>G	p.Asn396Ser	missense_variant	6/12	ENST00000402774.8	NP_001129665.1
FASTKD2	NM_001136194.2 linkuse as main transcript	c.1187A>G	p.Asn396Ser	missense_variant	6/12		NP_001129666.1
FASTKD2	NM_014929.4 linkuse as main transcript	c.1187A>G	p.Asn396Ser	missense_variant	6/12		NP_055744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASTKD2	ENST00000402774.8 linkuse as main transcript	c.1187A>G	p.Asn396Ser	missense_variant	6/12	1	NM_001136193.2	ENSP00000385990	P1	Q9NYY8-1
FASTKD2	ENST00000236980.10 linkuse as main transcript	c.1187A>G	p.Asn396Ser	missense_variant	6/12	1		ENSP00000236980	P1	Q9NYY8-1
FASTKD2	ENST00000403094.3 linkuse as main transcript	c.1187A>G	p.Asn396Ser	missense_variant	6/12	5		ENSP00000384929	P1	Q9NYY8-1
FASTKD2	ENST00000487777.5 linkuse as main transcript	n.1245A>G		non_coding_transcript_exon_variant	6/10	5

Frequencies

GnomAD3 genomes

AF:

0.00975

AC:

1485

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00240

AC:

602

AN:

251338

Hom.:

AF XY:

0.00178

AC XY:

242

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0326

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00102

AC:

1488

AN:

1461516

Hom.:

Cov.:

AF XY:

0.000915

AC XY:

665

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.0338

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000998

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00979

AC:

1492

AN:

152356

Hom.:

Cov.:

AF XY:

0.00935

AC XY:

697

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0328

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.0108

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0338

AC:

149

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00309

AC:

375

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 12, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mitochondrial complex IV deficiency, nuclear type 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

.;.;T

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Pathogenic

2.9

M;M;M

MutationTaster

Benign

0.79

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.66

MVP

0.41

MPC

0.61

ClinPred

0.052

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.099

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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