rs2768294

Positions:

• chr9-105607093-G-C
• chr9-105607093-G-T

Variant summary

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

The NM_001079802.2(FKTN):​c.648-726G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 151,792 control chromosomes in the GnomAD database, including 35,534 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 0.68 (35534 hom., cov: 32)
• Consequence: FKTN NM_001079802.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

Genes affected

FKTN (HGNC:3622): (fukutin) The protein encoded by this gene is a putative transmembrane protein that is localized to the cis-Golgi compartment, where it may be involved in the glycosylation of alpha-dystroglycan in skeletal muscle. The encoded protein is thought to be a glycosyltransferase and could play a role in brain development. Defects in this gene are a cause of Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), limb-girdle muscular dystrophy type 2M (LGMD2M), and dilated cardiomyopathy type 1X (CMD1X). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FKTN	NM_001079802.2	c.648-726G>C		intron_variant		ENST00000357998.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FKTN	ENST00000357998.10	c.648-726G>C		intron_variant		5	NM_001079802.2	P1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103177 AN: 151674 Hom.: 35488 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.558

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.680 AC: 103279 AN: 151792 Hom.: 35534 Cov.: 32 AF XY: 0.681 AC XY: 50505 AN XY: 74162

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.695

Alfa AF: 0.566 Hom.: 1735

Bravo AF: 0.693

Asia WGS AF: 0.639 AC: 2194 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.69

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: rs2768294; hg19: chr9-108369374;