chr2-151662138-G-T

Variant names:

Variant summary

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

The NM_001164508.2(NEB):c.5967C>A(p.Asn1989Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,608,920 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N1989N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

NEB
NM_001164508.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.18

Publications

0 publications found

Variant links:

Genes affected

NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

NEB Gene-Disease associations (from GenCC):

nemaline myopathy 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal dominant nebulin-related myopathy
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
childhood-onset nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
intermediate nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
typical nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
lethal multiple pterygium syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
severe congenital nemaline myopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NEB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164508.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEB	NM_001164507.2	MANE Plus Clinical	c.5967C>A	p.Asn1989Lys	missense	Exon 46 of 182	NP_001157979.2	P20929-3
NEB	NM_001164508.2	MANE Select	c.5967C>A	p.Asn1989Lys	missense	Exon 46 of 182	NP_001157980.2	P20929-2
NEB	NM_001271208.2		c.5967C>A	p.Asn1989Lys	missense	Exon 46 of 183	NP_001258137.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEB	ENST00000397345.8	TSL:5 MANE Select	c.5967C>A	p.Asn1989Lys	missense	Exon 46 of 182	ENSP00000380505.3	P20929-2
NEB	ENST00000427231.7	TSL:5 MANE Plus Clinical	c.5967C>A	p.Asn1989Lys	missense	Exon 46 of 182	ENSP00000416578.2	P20929-3
NEB	ENST00000409198.5	TSL:5	c.5967C>A	p.Asn1989Lys	missense	Exon 46 of 150	ENSP00000386259.1	P20929-4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000808

AC:

AN:

247428

AF XY:

0.00000745

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1456892

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33334

American (AMR)

AF:

0.00

AC:

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.0000307

AC:

AN:

1108288

Other (OTH)

AF:

0.00

AC:

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41398

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2090

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

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

0.12

Eigen_PC

Benign

0.028

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.074

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.3

PhyloP100

2.2

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.27

Sift

Uncertain

0.012

Sift4G

Uncertain

0.0040

Polyphen

0.97

Vest4

0.59

MutPred

0.77

Gain of ubiquitination at N1989 (P = 0.0289)

MVP

0.58

MPC

0.31

ClinPred

0.86

GERP RS

2.1

Varity_R

0.26

gMVP

0.63

Mutation Taster

=77/23

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over