rs2518108

Variant names:

• chr9-105643816-A-T
• rs2518108
• ENST00000676310.1:c.1271-8256A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000676310.1(FKTN):​c.1271-8256A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,106 control chromosomes in the GnomAD database, including 12,630 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 0.39 (12630 hom., cov: 33)
• Consequence: FKTN ENST00000676310.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000676310.1	c.1271-8256A>T		intron_variant	Intron 9 of 9			ENSP00000501585.1
FKTN	ENST00000674633.1	c.1271-888A>T		intron_variant	Intron 9 of 9			ENSP00000502164.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60020 AN: 151988 Hom.: 12607 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.395 AC: 60075 AN: 152106 Hom.: 12630 Cov.: 33 AF XY: 0.392 AC XY: 29168 AN XY: 74340

African (AFR) AF: 0.265 AC: 10997 AN: 41498

American (AMR) AF: 0.519 AC: 7933 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1624 AN: 3470

East Asian (EAS) AF: 0.272 AC: 1409 AN: 5182

South Asian (SAS) AF: 0.261 AC: 1258 AN: 4818

European-Finnish (FIN) AF: 0.421 AC: 4449 AN: 10568

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31050 AN: 67966

Other (OTH) AF: 0.433 AC: 916 AN: 2116

Alfa AF: 0.437 Hom.: 1822

Bravo AF: 0.399

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.77
PhyloP100		-0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2518108; hg19: chr9-108406097;