rs2766999

Variant names:

• chr9-110787888-T-C
• rs2766999
• NM_005592.4:c.1927+50T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-110787888-T-C
• chr9-110787888-T-A
• chr9-110787888-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005592.4(MUSK):​c.1927+50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,563,634 control chromosomes in the GnomAD database, including 172,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17382 hom., cov: 31)
  • Exomes 𝑓: 0.46 (154802 hom.)
• Consequence: MUSK NM_005592.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.220
• Publications: 6 publications found

Genes affected

MUSK (HGNC:7525): (muscle associated receptor tyrosine kinase) This gene encodes a muscle-specific tyrosine kinase receptor. The encoded protein may play a role in clustering of the acetylcholine receptor in the postsynaptic neuromuscular junction. Mutations in this gene have been associated with congenital myasthenic syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Oct 2009]

MUSK Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 9

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-110787888-T-C is Benign according to our data. Variant chr9-110787888-T-C is described in ClinVar as Benign. ClinVar VariationId is 259804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005592.4. 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
	MUSK	NM_005592.4	MANE Select	c.1927+50T>C		intron	N/A	NP_005583.1	O15146-1
	MUSK	NM_001166280.2		c.1669+50T>C		intron	N/A	NP_001159752.1	O15146-2
	MUSK	NM_001166281.2		c.1639+50T>C		intron	N/A	NP_001159753.1	O15146-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUSK	ENST00000374448.9	TSL:5 MANE Select	c.1927+50T>C		intron	N/A	ENSP00000363571.4	O15146-1
	MUSK	ENST00000416899.7	TSL:5	c.1903+50T>C		intron	N/A	ENSP00000393608.3	A0A087WSY1
	MUSK	ENST00000189978.10	TSL:5	c.1669+50T>C		intron	N/A	ENSP00000189978.6	O15146-2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71492 AN: 151854 Hom.: 17362 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.496

GnomAD2 exomes AF: 0.425 AC: 77509 AN: 182458 AF XY: 0.427

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.313

Gnomad ASJ exome AF: 0.583

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.514

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.460

GnomAD4 exome AF: 0.462 AC: 652097 AN: 1411662 Hom.: 154802 Cov.: 27 AF XY: 0.459 AC XY: 320555 AN XY: 698290

African (AFR) AF: 0.523 AC: 16965 AN: 32440

American (AMR) AF: 0.319 AC: 11906 AN: 37374

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 14770 AN: 25314

East Asian (EAS) AF: 0.145 AC: 5484 AN: 37806

South Asian (SAS) AF: 0.353 AC: 28414 AN: 80504

European-Finnish (FIN) AF: 0.511 AC: 26037 AN: 50982

Middle Eastern (MID) AF: 0.546 AC: 3116 AN: 5704

European-Non Finnish (NFE) AF: 0.478 AC: 517932 AN: 1082878

Other (OTH) AF: 0.468 AC: 27473 AN: 58660

GnomAD4 genome AF: 0.471 AC: 71563 AN: 151972 Hom.: 17382 Cov.: 31 AF XY: 0.470 AC XY: 34945 AN XY: 74288

African (AFR) AF: 0.518 AC: 21451 AN: 41428

American (AMR) AF: 0.395 AC: 6026 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3470

East Asian (EAS) AF: 0.126 AC: 650 AN: 5162

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4812

European-Finnish (FIN) AF: 0.521 AC: 5504 AN: 10560

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.482 AC: 32763 AN: 67956

Other (OTH) AF: 0.495 AC: 1045 AN: 2112

Alfa AF: 0.466 Hom.: 7009

Bravo AF: 0.464

Asia WGS AF: 0.253 AC: 885 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.7
DANN	Benign	0.53
PhyloP100		-0.22
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: rs2766999; hg19: chr9-113550168; COSMIC: COSV51893576;