chr2-206769512-T-A

Variant names:

• chr2-206769512-T-A
• rs2277912
• NM_001136193.2:c.778-579T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136193.2(FASTKD2):​c.778-579T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: FASTKD2 NM_001136193.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 18 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASTKD2	NM_001136193.2	c.778-579T>A		intron_variant	Intron 2 of 11	ENST00000402774.8	NP_001129665.1
FASTKD2	NM_001136194.2	c.778-579T>A		intron_variant	Intron 2 of 11		NP_001129666.1
FASTKD2	NM_014929.4	c.778-579T>A		intron_variant	Intron 2 of 11		NP_055744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASTKD2	ENST00000402774.8	c.778-579T>A		intron_variant	Intron 2 of 11	1	NM_001136193.2	ENSP00000385990.3
FASTKD2	ENST00000236980.10	c.778-579T>A		intron_variant	Intron 2 of 11	1		ENSP00000236980.6
FASTKD2	ENST00000403094.3	c.778-579T>A		intron_variant	Intron 2 of 11	5		ENSP00000384929.3
FASTKD2	ENST00000487777.5	n.836-579T>A		intron_variant	Intron 2 of 9	5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.94
DANN	Benign	0.51
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2277912; hg19: chr2-207634236;