Genetic Variant MYO9A:p.Arg2461Pro (chr15-71826845-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006901.4(MYO9A):c.7382G>C(p.Arg2461Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2461Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYO9A
NM_006901.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.32

Publications

0 publications found

Variant links:

Genes affected

MYO9A (HGNC:7608): (myosin IXA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). Unconventional myosins contain the basic domains of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with Bardet-Biedl Syndrome. [provided by RefSeq, Dec 2011]

MYO9A Gene-Disease associations (from GenCC):

myasthenic syndrome, congenital, 24, presynaptic
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, PanelApp Australia, Labcorp Genetics (formerly Invitae)
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arthrogryposis syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

MYO9A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO9A	NM_006901.4 link	c.7382G>C	p.Arg2461Pro	missense_variant	Exon 42 of 42	ENST00000356056.10	NP_008832.2	B2RTY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO9A	ENST00000356056.10 link	c.7382G>C	p.Arg2461Pro	missense_variant	Exon 42 of 42	1	NM_006901.4	ENSP00000348349.5	B2RTY4-1
MYO9A	ENST00000561618.5 link	c.3929G>C	p.Arg1310Pro	missense_variant	Exon 19 of 19	1		ENSP00000457945.1	H3BV44
MYO9A	ENST00000564571.5 link	c.*187G>C		3_prime_UTR_variant	Exon 42 of 42	1		ENSP00000456192.1	H3BRD5
MYO9A	ENST00000568042.5 link	c.1124G>C	p.Arg375Pro	missense_variant	Exon 9 of 9	5		ENSP00000457407.1	H3BU05

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111950

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

.;D

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Uncertain

2.2

M;M

PhyloP100

4.3

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.33

N;.

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.17

T;T

Polyphen

1.0

D;D

Vest4

0.49

MutPred

0.54

Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);

MVP

0.20

MPC

0.60

ClinPred

0.97

GERP RS

5.4

Varity_R

0.38

gMVP

0.32

Mutation Taster

=41/59

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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15-71826845-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over