9-105607093-G-C

Variant names:

• chr9-105607093-G-C
• rs2768294
• NM_001079802.2:c.648-726G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

FKTN Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy type 2M

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• myopathy caused by variation in FKTN

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy without intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscle-eye-brain disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy 1X

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FKTN	NM_001079802.2	c.648-726G>C		intron_variant	Intron 6 of 10	ENST00000357998.10	NP_001073270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000357998.10	c.648-726G>C		intron_variant	Intron 6 of 10	5	NM_001079802.2	ENSP00000350687.6

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

African (AFR) AF: 0.749 AC: 31043 AN: 41446

American (AMR) AF: 0.769 AC: 11729 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2271 AN: 3468

East Asian (EAS) AF: 0.733 AC: 3792 AN: 5174

South Asian (SAS) AF: 0.556 AC: 2671 AN: 4806

European-Finnish (FIN) AF: 0.662 AC: 6961 AN: 10512

Middle Eastern (MID) AF: 0.573 AC: 165 AN: 288

European-Non Finnish (NFE) AF: 0.630 AC: 42716 AN: 67836

Other (OTH) AF: 0.695 AC: 1461 AN: 2102

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
PhyloP100		-0.48
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: rs2768294; hg19: chr9-108369374;