NM_001079802.2:c.1172+1456T>A

Variant names:

• chr9-105621517-T-A
• rs2518131
• NM_001079802.2:c.1172+1456T>A

Variant summary

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

The NM_001079802.2(FKTN):​c.1172+1456T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 151,896 control chromosomes in the GnomAD database, including 35,820 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 (35820 hom., cov: 31)
• Consequence: FKTN NM_001079802.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 1 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=-1.08).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKTN	NM_001079802.2	c.1172+1456T>A		intron_variant	Intron 10 of 10	ENST00000357998.10	NP_001073270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000357998.10	c.1172+1456T>A		intron_variant	Intron 10 of 10	5	NM_001079802.2	ENSP00000350687.6

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103600 AN: 151778 Hom.: 35772 Cov.: 31

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.683 AC: 103704 AN: 151896 Hom.: 35820 Cov.: 31 AF XY: 0.683 AC XY: 50720 AN XY: 74242

African (AFR) AF: 0.757 AC: 31382 AN: 41448

American (AMR) AF: 0.770 AC: 11757 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2284 AN: 3470

East Asian (EAS) AF: 0.733 AC: 3793 AN: 5176

South Asian (SAS) AF: 0.555 AC: 2668 AN: 4808

European-Finnish (FIN) AF: 0.662 AC: 6982 AN: 10546

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.630 AC: 42733 AN: 67872

Other (OTH) AF: 0.695 AC: 1466 AN: 2110

Alfa AF: 0.660 Hom.: 4136

Bravo AF: 0.696

Asia WGS AF: 0.639 AC: 2227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.7
DANN	Benign	0.11
PhyloP100		-1.7
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: rs2518131; hg19: chr9-108383798;