rs2072797

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.2011G>A(p.Gly671Ser) variant causes a missense change. The variant allele was found at a frequency of 0.11 in 1,613,644 control chromosomes in the GnomAD database, including 10,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G671G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.090 ( 831 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9850 hom. )

Consequence

SUN2
NM_015374.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.80

Publications

37 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:

GTPBP1 (HGNC:4669): (GTP binding protein 1) This gene is upregulated by interferon-gamma and encodes a protein that is a member of the AGP11/GTPBP1 family of GTP-binding proteins. A structurally similar protein has been found in mouse, where disruption of the gene for that protein had no observable phenotype. [provided by RefSeq, Jul 2008]

GTPBP1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1
Inheritance: AR Classification: MODERATE Submitted by: G2P

GTPBP1 links:

ENSG00000230149 (HGNC:):

ENSG00000230149 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=0.0016545057).

BP6

Variant 22-38738202-C-T is Benign according to our data. Variant chr22-38738202-C-T is described in ClinVar as Benign. ClinVar VariationId is 1168063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN2	NM_015374.3 link	c.2011G>A	p.Gly671Ser	missense_variant	Exon 17 of 18	ENST00000689035.1	NP_056189.1	Q9UH99-1A0A024R1P7B4E2A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN2	ENST00000689035.1 link	c.2011G>A	p.Gly671Ser	missense_variant	Exon 17 of 18		NM_015374.3	ENSP00000508608.1		Q9UH99-1

Frequencies

GnomAD3 genomes

AF:

0.0900

AC:

13689

AN:

152030

Hom.:

834

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0208

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.0678

Gnomad ASJ

AF:

0.0919

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.0906

GnomAD2 exomes

AF:

0.109

AC:

27287

AN:

251384

AF XY:

0.112

show subpopulations

Gnomad AFR exome

AF:

0.0173

Gnomad AMR exome

AF:

0.0458

Gnomad ASJ exome

AF:

0.0866

Gnomad EAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.112

AC:

164218

AN:

1461496

Hom.:

9850

Cov.:

AF XY:

0.113

AC XY:

81885

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.0171

AC:

572

AN:

33478

American (AMR)

AF:

0.0495

AC:

2215

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0925

AC:

2418

AN:

26132

East Asian (EAS)

AF:

0.160

AC:

6335

AN:

39694

South Asian (SAS)

AF:

0.121

AC:

10403

AN:

86248

European-Finnish (FIN)

AF:

0.160

AC:

8522

AN:

53252

Middle Eastern (MID)

AF:

0.101

AC:

585

AN:

5768

European-Non Finnish (NFE)

AF:

0.114

AC:

126735

AN:

1111814

Other (OTH)

AF:

0.107

AC:

6433

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

7984

15969

23953

31938

39922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4612

9224

13836

18448

23060

<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:

0.0899

AC:

13680

AN:

152148

Hom.:

831

Cov.:

AF XY:

0.0925

AC XY:

6881

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0207

AC:

861

AN:

41518

American (AMR)

AF:

0.0677

AC:

1035

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0919

AC:

319

AN:

3470

East Asian (EAS)

AF:

0.165

AC:

852

AN:

5168

South Asian (SAS)

AF:

0.126

AC:

609

AN:

4822

European-Finnish (FIN)

AF:

0.161

AC:

1699

AN:

10576

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7858

AN:

67990

Other (OTH)

AF:

0.0897

AC:

189

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

650

1300

1950

2600

3250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.103

Hom.:

2632

Bravo

AF:

0.0823

TwinsUK

AF:

0.115

AC:

427

ALSPAC

AF:

0.124

AC:

477

ESP6500AA

AF:

0.0213

AC:

ESP6500EA

AF:

0.114

AC:

977

ExAC

AF:

0.109

AC:

13251

Asia WGS

AF:

0.137

AC:

479

AN:

3478

EpiCase

AF:

0.113

EpiControl

AF:

0.115

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 17827388) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Emery-Dreifuss muscular dystrophy

Benign:1

Feb 03, 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

0.19

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;T;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.76

.;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

L;.;L;.

PhyloP100

5.8

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-5.5

D;D;D;D

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.021

D;D;D;D

Polyphen

0.35

B;.;B;.

Vest4

0.28

MPC

0.69

ClinPred

0.046

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.86

gMVP

0.74

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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