rs17309806

Variant names:

• chr9-105618074-C-A
• rs17309806
• NM_001079802.2:c.1026C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-105618074-C-A
• chr9-105618074-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001079802.2(FKTN):​c.1026C>A​(p.Leu342Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,606,314 control chromosomes in the GnomAD database, including 70,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L342L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.27 (5818 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64747 hom.)
• Consequence: FKTN NM_001079802.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:16
• Conservation: PhyloP100: 0.635
• Publications: 22 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 9-105618074-C-A is Benign according to our data. Variant chr9-105618074-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.635 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FKTN	NM_001079802.2	c.1026C>A	p.Leu342Leu	synonymous_variant	Exon 9 of 11	ENST00000357998.10	NP_001073270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FKTN	ENST00000357998.10	c.1026C>A	p.Leu342Leu	synonymous_variant	Exon 9 of 11	5	NM_001079802.2	ENSP00000350687.6

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41066 AN: 151948 Hom.: 5809 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.0947

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.276

GnomAD2 exomes AF: 0.253 AC: 63477 AN: 250748 AF XY: 0.247

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.0915

Gnomad FIN exome AF: 0.279

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.290 AC: 421143 AN: 1454250 Hom.: 64747 Cov.: 30 AF XY: 0.284 AC XY: 205289 AN XY: 723890

African (AFR) AF: 0.235 AC: 7850 AN: 33334

American (AMR) AF: 0.279 AC: 12483 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 7369 AN: 26078

East Asian (EAS) AF: 0.102 AC: 4034 AN: 39650

South Asian (SAS) AF: 0.0982 AC: 8468 AN: 86196

European-Finnish (FIN) AF: 0.286 AC: 15275 AN: 53398

Middle Eastern (MID) AF: 0.191 AC: 1099 AN: 5754

European-Non Finnish (NFE) AF: 0.315 AC: 347938 AN: 1104958

Other (OTH) AF: 0.276 AC: 16627 AN: 60174

GnomAD4 genome AF: 0.270 AC: 41114 AN: 152064 Hom.: 5818 Cov.: 32 AF XY: 0.265 AC XY: 19708 AN XY: 74346

African (AFR) AF: 0.236 AC: 9801 AN: 41456

American (AMR) AF: 0.291 AC: 4441 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3468

East Asian (EAS) AF: 0.0954 AC: 495 AN: 5186

South Asian (SAS) AF: 0.105 AC: 507 AN: 4816

European-Finnish (FIN) AF: 0.275 AC: 2902 AN: 10568

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21161 AN: 67970

Other (OTH) AF: 0.277 AC: 584 AN: 2110

Alfa AF: 0.295 Hom.: 28254

Bravo AF: 0.269

Asia WGS AF: 0.126 AC: 438 AN: 3478

EpiCase AF: 0.304

EpiControl AF: 0.299

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:16

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:10

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Leu342Leu in exon 9 of FKTN: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 31.8% (2731/8596) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17309806). -

May 26, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 16, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1X Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Cardiovascular phenotype Benign:1

Mar 11, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Walker-Warburg congenital muscular dystrophy Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	7.0
DANN	Benign	0.65
PhyloP100		0.64
PromoterAI		-0.021	Neutral
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: rs17309806; hg19: chr9-108380355; COSMIC: COSV56311244; COSMIC: COSV56311244;