chr2-206765582-T-C

Variant names:

• chr2-206765582-T-C
• rs886055504
• ENST00000236980.10:c.-123T>C

Variant summary

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

The ENST00000236980.10(FASTKD2):​c.-123T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000107 in 932,836 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: FASTKD2 ENST00000236980.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 0 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=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASTKD2	NM_001136193.2	c.-216T>C		upstream_gene_variant		ENST00000402774.8	NP_001129665.1
FASTKD2	NM_001136194.2	c.-231T>C		upstream_gene_variant			NP_001129666.1
FASTKD2	NM_014929.4	c.-123T>C		upstream_gene_variant			NP_055744.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASTKD2	ENST00000402774.8	c.-216T>C		upstream_gene_variant		1	NM_001136193.2	ENSP00000385990.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000107 AC: 1 AN: 932836 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 437534

African (AFR) AF: 0.00 AC: 0 AN: 18950

American (AMR) AF: 0.00 AC: 0 AN: 4212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9786

East Asian (EAS) AF: 0.00 AC: 0 AN: 12296

South Asian (SAS) AF: 0.00 AC: 0 AN: 23210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2276

European-Non Finnish (NFE) AF: 0.00000122 AC: 1 AN: 819220

Other (OTH) AF: 0.00 AC: 0 AN: 34760

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.65
PhyloP100		3.3
PromoterAI		-0.53	Under-expression

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: rs886055504; hg19: chr2-207630306;