chr2-206781950-A-G

Variant names:

• chr2-206781950-A-G
• rs7594645
• NM_001136193.2:c.1428-4783A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• combined oxidative phosphorylation deficiency 44

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• FASTKD2-related infantile mitochondrial encephalomyopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FASTKD2	NM_001136193.2	c.1428-4783A>G		intron_variant	Intron 7 of 11	ENST00000402774.8	NP_001129665.1
FASTKD2	NM_001136194.2	c.1428-4783A>G		intron_variant	Intron 7 of 11		NP_001129666.1
FASTKD2	NM_014929.4	c.1428-4783A>G		intron_variant	Intron 7 of 11		NP_055744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASTKD2	ENST00000402774.8	c.1428-4783A>G		intron_variant	Intron 7 of 11	1	NM_001136193.2	ENSP00000385990.3
FASTKD2	ENST00000236980.10	c.1428-4783A>G		intron_variant	Intron 7 of 11	1		ENSP00000236980.6
FASTKD2	ENST00000403094.3	c.1428-4783A>G		intron_variant	Intron 7 of 11	5		ENSP00000384929.3
FASTKD2	ENST00000487777.5	n.1486-4783A>G		intron_variant	Intron 7 of 9	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

African (AFR) AF: 0.134 AC: 5551 AN: 41502

American (AMR) AF: 0.0545 AC: 833 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0331 AC: 115 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4824

European-Finnish (FIN) AF: 0.0462 AC: 490 AN: 10604

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0620 AC: 4214 AN: 68002

Other (OTH) AF: 0.0749 AC: 158 AN: 2110

Alfa AF: 0.0640 Hom.: 631

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
PhyloP100		0.066
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7594645; hg19: chr2-207646674;