2-206766567-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001136193.2(FASTKD2):c.-50-77C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 852,806 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (2 hom.)
• Consequence: FASTKD2 NM_001136193.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-206766567-C-A is Benign according to our data. Variant chr2-206766567-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1200903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00476 (724/152250) while in subpopulation AFR AF= 0.0169 (704/41570). AF 95% confidence interval is 0.0159. There are 4 homozygotes in gnomad4. There are 315 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASTKD2	NM_001136193.2	c.-50-77C>A		intron_variant		ENST00000402774.8
FASTKD2	NM_001136194.2	c.-50-77C>A		intron_variant
FASTKD2	NM_014929.4	c.-50-77C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASTKD2	ENST00000402774.8	c.-50-77C>A		intron_variant		1	NM_001136193.2	P1

Frequencies

GnomAD3 genomes AF: 0.00476 AC: 724 AN: 152132 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000465 AC: 326 AN: 700556 Hom.: 2 AF XY: 0.000397 AC XY: 148 AN XY: 372612

Gnomad4 AFR exome AF: 0.0155

Gnomad4 AMR exome AF: 0.000778

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000644

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000177

Gnomad4 OTH exome AF: 0.000721

GnomAD4 genome AF: 0.00476 AC: 724 AN: 152250 Hom.: 4 Cov.: 32 AF XY: 0.00423 AC XY: 315 AN XY: 74438

Gnomad4 AFR AF: 0.0169

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00395 Hom.: 0

Bravo AF: 0.00518

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.7
Dann	Benign	0.75

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: rs140026989; hg19: chr2-207631291;