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: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079802.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKTN	NM_001079802.2	MANE Select	c.1026C>A	p.Leu342Leu	synonymous	Exon 9 of 11	NP_001073270.1	O75072-1
	FKTN	NM_001351496.2		c.1026C>A	p.Leu342Leu	synonymous	Exon 10 of 12	NP_001338425.1	O75072-1
	FKTN	NM_006731.2		c.1026C>A	p.Leu342Leu	synonymous	Exon 8 of 10	NP_006722.2	O75072-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKTN	ENST00000357998.10	TSL:5 MANE Select	c.1026C>A	p.Leu342Leu	synonymous	Exon 9 of 11	ENSP00000350687.6	O75072-1
	FKTN	ENST00000223528.6	TSL:1	c.1026C>A	p.Leu342Leu	synonymous	Exon 8 of 10	ENSP00000223528.2	O75072-1
	FKTN	ENST00000602526.1	TSL:1	n.*1064C>A		non_coding_transcript_exon	Exon 9 of 11	ENSP00000473347.1	R4GMU0

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	10	not specified (10)
-	-	2	not provided (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Dilated cardiomyopathy 1X (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 (1)
-	-	1	Walker-Warburg congenital muscular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

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;