rs2072799

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015374.3(SUN2):c.97A>G(p.Thr33Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00608 in 1,613,768 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 86 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 599 hom. )

Consequence

SUN2
NM_015374.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.170

Publications

13 publications found

Variant links:

Genes affected

SUN2 (HGNC:14210): (Sad1 and UNC84 domain containing 2) SUN1 (MIM 607723) and SUN2 are inner nuclear membrane (INM) proteins that play a major role in nuclear-cytoplasmic connection by formation of a 'bridge' across the nuclear envelope, known as the LINC complex, via interaction with the conserved luminal KASH domain of nesprins (e.g., SYNE1; MIM 608441) located in the outer nuclear membrane (ONM). The LINC complex provides a direct connection between the nuclear lamina and the cytoskeleton, which contributes to nuclear positioning and cellular rigidity (summary by Haque et al., 2010 [PubMed 19933576]).[supplied by OMIM, Nov 2010]

SUN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0013588965).

BP6

Variant 22-38752532-T-C is Benign according to our data. Variant chr22-38752532-T-C is described in ClinVar as Benign. ClinVar VariationId is 461693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN2	NM_015374.3 link	c.97A>G	p.Thr33Ala	missense_variant	Exon 2 of 18	ENST00000689035.1	NP_056189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN2	ENST00000689035.1 link	c.97A>G	p.Thr33Ala	missense_variant	Exon 2 of 18		NM_015374.3	ENSP00000508608.1

Frequencies

GnomAD3 genomes

AF:

0.00791

AC:

1204

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00960

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.0150

AC:

3748

AN:

249948

AF XY:

0.0140

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.00946

Gnomad NFE exome

AF:

0.000738

Gnomad OTH exome

AF:

0.00965

GnomAD4 exome

AF:

0.00589

AC:

8607

AN:

1461438

Hom.:

599

Cov.:

AF XY:

0.00574

AC XY:

4176

AN XY:

727010

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33470

American (AMR)

AF:

0.00152

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

26126

East Asian (EAS)

AF:

0.166

AC:

6601

AN:

39700

South Asian (SAS)

AF:

0.00260

AC:

224

AN:

86240

European-Finnish (FIN)

AF:

0.00874

AC:

466

AN:

53320

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000486

AC:

540

AN:

1111746

Other (OTH)

AF:

0.0109

AC:

656

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

379

758

1138

1517

1896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<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:

0.00790

AC:

1204

AN:

152330

Hom.:

Cov.:

AF XY:

0.00885

AC XY:

659

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41576

American (AMR)

AF:

0.00327

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.177

AC:

918

AN:

5180

South Asian (SAS)

AF:

0.00414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00960

AC:

102

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000808

AC:

AN:

68028

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

109

164

218

273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00660

Hom.:

161

Bravo

AF:

0.00795

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0143

AC:

1737

Asia WGS

AF:

0.0570

AC:

197

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Emery-Dreifuss muscular dystrophy

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.050

T;.;T;.;.;.;.;.;.;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.49

.;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L;.;.;.;.;.;.;.

PhyloP100

-0.17

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.0

N;N;N;N;N;D;D;D;D;D

REVEL

Benign

0.14

Sift

Benign

0.14

T;T;T;T;T;D;T;T;D;T

Sift4G

Benign

0.067

T;T;T;T;.;.;.;T;.;.

Polyphen

0.14

B;.;B;.;.;.;.;.;.;.

Vest4

0.036

MPC

0.23

ClinPred

0.0029

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.26

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over