dbSNP rs2987346: MTUS2:p.Asp527Gly (chr13-29026278-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001033602.4(MTUS2):c.1580A>G(p.Asp527Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,613,792 control chromosomes in the GnomAD database, including 3,412 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.093 ( 1506 hom., cov: 32)

Exomes 𝑓: 0.028 ( 1906 hom. )

Consequence

MTUS2
NM_001033602.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.880

Publications

11 publications found

Variant links:

Genes affected

MTUS2 (HGNC:20595): (microtubule associated scaffold protein 2) Enables microtubule binding activity and protein homodimerization activity. Part of nucleus. Colocalizes with centrosome and cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

MTUS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006790191).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTUS2	NM_001033602.4 link	c.1580A>G	p.Asp527Gly	missense_variant	Exon 3 of 16	ENST00000612955.6	NP_001028774.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTUS2	ENST00000612955.6 link	c.1580A>G	p.Asp527Gly	missense_variant	Exon 3 of 16	5	NM_001033602.4	ENSP00000483729.2		Q5JR59-2

Frequencies

GnomAD3 genomes

AF:

0.0928

AC:

14096

AN:

151970

Hom.:

1488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0523

Gnomad ASJ

AF:

0.0268

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0882

GnomAD2 exomes

AF:

0.0442

AC:

10999

AN:

249128

AF XY:

0.0391

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.0292

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.0205

Gnomad OTH exome

AF:

0.0374

GnomAD4 exome

AF:

0.0283

AC:

41322

AN:

1461704

Hom.:

1906

Cov.:

AF XY:

0.0272

AC XY:

19749

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.276

AC:

9243

AN:

33480

American (AMR)

AF:

0.0327

AC:

1462

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

821

AN:

26136

East Asian (EAS)

AF:

0.0978

AC:

3884

AN:

39698

South Asian (SAS)

AF:

0.0132

AC:

1135

AN:

86258

European-Finnish (FIN)

AF:

0.0110

AC:

590

AN:

53402

Middle Eastern (MID)

AF:

0.0576

AC:

332

AN:

5768

European-Non Finnish (NFE)

AF:

0.0189

AC:

21016

AN:

1111866

Other (OTH)

AF:

0.0470

AC:

2839

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

2606

5212

7817

10423

13029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1002

2004

3006

4008

5010

<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:

0.0930

AC:

14147

AN:

152088

Hom.:

1506

Cov.:

AF XY:

0.0908

AC XY:

6752

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.262

AC:

10871

AN:

41432

American (AMR)

AF:

0.0523

AC:

799

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0268

AC:

AN:

3470

East Asian (EAS)

AF:

0.113

AC:

583

AN:

5158

South Asian (SAS)

AF:

0.0189

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0112

AC:

119

AN:

10610

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0203

AC:

1382

AN:

67996

Other (OTH)

AF:

0.0882

AC:

186

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

563

1126

1690

2253

2816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0389

Hom.:

1364

Bravo

AF:

0.106

TwinsUK

AF:

0.0208

AC:

ALSPAC

AF:

0.0166

AC:

ESP6500AA

AF:

0.250

AC:

1010

ESP6500EA

AF:

0.0190

AC:

159

ExAC

AF:

0.0473

AC:

5717

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

EpiCase

AF:

0.0242

EpiControl

AF:

0.0260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.9

(source)

DANN

Benign

0.78

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.90

PhyloP100

0.88

PrimateAI

Benign

0.25

Sift4G

Benign

0.15

Vest4

0.035

ClinPred

0.00085

GERP RS

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over