rs141447598

chr2-206766842-A-Cchr2-206766842-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136193.2(FASTKD2):c.149A>C(p.Lys50Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K50R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FASTKD2 NM_001136193.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611

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]

ACMG classification

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=0.16486093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASTKD2	NM_001136193.2	c.149A>C	p.Lys50Thr	missense_variant	2/12	ENST00000402774.8
FASTKD2	NM_001136194.2	c.149A>C	p.Lys50Thr	missense_variant	2/12
FASTKD2	NM_014929.4	c.149A>C	p.Lys50Thr	missense_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASTKD2	ENST00000402774.8	c.149A>C	p.Lys50Thr	missense_variant	2/12	1	NM_001136193.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248234 Hom.: 0 AF XY: 0.00000745 AC XY: 1 AN XY: 134154

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.000166

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456752 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723948

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	16
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0017	T;T;T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L;.;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N;D;N;N
REVEL	Benign	0.062
Sift	Benign	0.043	D;D;D;D
Sift4G	Uncertain	0.047	D;D;D;D
Polyphen		0.79	P;.;P;P
Vest4		0.19
MutPred		0.45		Loss of methylation at K50 (P = 0.0011);Loss of methylation at K50 (P = 0.0011);Loss of methylation at K50 (P = 0.0011);Loss of methylation at K50 (P = 0.0011);
MVP		0.52
MPC		0.20
ClinPred		0.15	T
GERP RS		0.69
Varity_R		0.082
gMVP		0.18

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

Other links and lift over

dbSNP: rs141447598; hg19: chr2-207631566;