rs7594645

Positions:

• chr2-206781950-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136193.2(FASTKD2):​c.1428-4783A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.076 in 152,174 control chromosomes in the GnomAD database, including 558 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.076 (558 hom., cov: 31)
• Consequence: FASTKD2 NM_001136193.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0660

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASTKD2	NM_001136193.2	c.1428-4783A>G		intron_variant		ENST00000402774.8
FASTKD2	NM_001136194.2	c.1428-4783A>G		intron_variant
FASTKD2	NM_014929.4	c.1428-4783A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASTKD2	ENST00000402774.8	c.1428-4783A>G		intron_variant		1	NM_001136193.2	P1
FASTKD2	ENST00000236980.10	c.1428-4783A>G		intron_variant		1		P1
FASTKD2	ENST00000403094.3	c.1428-4783A>G		intron_variant		5		P1
FASTKD2	ENST00000487777.5	n.1486-4783A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11552 AN: 152056 Hom.: 556 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.0331

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.0462

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0761

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0760 AC: 11572 AN: 152174 Hom.: 558 Cov.: 31 AF XY: 0.0744 AC XY: 5532 AN XY: 74390

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.0331

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.0462

Gnomad4 NFE AF: 0.0620

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0664 Hom.: 69

Bravo AF: 0.0812

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.49

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: rs7594645; hg19: chr2-207646674;