rs138708

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1042C>T(p.Arg348Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0216 in 1,605,716 control chromosomes in the GnomAD database, including 733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R348H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.017 ( 49 hom., cov: 32)

Exomes 𝑓: 0.022 ( 684 hom. )

Consequence

SUN2
NM_015374.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.99

Publications

22 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:

ENSG00000225450 (HGNC:):

ENSG00000225450 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=0.0023243427).

BP6

Variant 22-38742327-G-A is Benign according to our data. Variant chr22-38742327-G-A is described in ClinVar as Benign. ClinVar VariationId is 461670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN2	NM_015374.3 link	c.1042C>T	p.Arg348Cys	missense_variant	Exon 9 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.1042C>T	p.Arg348Cys	missense_variant	Exon 9 of 18		NM_015374.3	ENSP00000508608.1

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2602

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00661

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.0983

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0200

Gnomad OTH

AF:

0.0187

GnomAD2 exomes

AF:

0.0216

AC:

5397

AN:

249838

AF XY:

0.0214

show subpopulations

Gnomad AFR exome

AF:

0.00672

Gnomad AMR exome

AF:

0.00816

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.0932

Gnomad FIN exome

AF:

0.00686

Gnomad NFE exome

AF:

0.0210

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0220

AC:

32007

AN:

1453484

Hom.:

684

Cov.:

AF XY:

0.0217

AC XY:

15624

AN XY:

721264

show subpopulations

African (AFR)

AF:

0.00530

AC:

177

AN:

33366

American (AMR)

AF:

0.00964

AC:

429

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.0241

AC:

628

AN:

26014

East Asian (EAS)

AF:

0.131

AC:

5156

AN:

39424

South Asian (SAS)

AF:

0.0130

AC:

1122

AN:

86056

European-Finnish (FIN)

AF:

0.00693

AC:

366

AN:

52834

Middle Eastern (MID)

AF:

0.0256

AC:

147

AN:

5734

European-Non Finnish (NFE)

AF:

0.0205

AC:

22678

AN:

1105566

Other (OTH)

AF:

0.0217

AC:

1304

AN:

59966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1759

3518

5278

7037

8796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.0171

AC:

2603

AN:

152232

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1235

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00659

AC:

274

AN:

41554

American (AMR)

AF:

0.0121

AC:

185

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3470

East Asian (EAS)

AF:

0.0983

AC:

507

AN:

5156

South Asian (SAS)

AF:

0.0201

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00480

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0200

AC:

1359

AN:

68010

Other (OTH)

AF:

0.0194

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

119

239

358

478

597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0222

Hom.:

222

Bravo

AF:

0.0178

TwinsUK

AF:

0.0202

AC:

ALSPAC

AF:

0.0189

AC:

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0200

AC:

172

ExAC

AF:

0.0221

AC:

2680

Asia WGS

AF:

0.0500

AC:

173

AN:

3478

EpiCase

AF:

0.0194

EpiControl

AF:

0.0228

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

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

0.15

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

T;.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

.;D;D

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.4

M;.;M

PhyloP100

6.0

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.025

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.32

MPC

0.92

ClinPred

0.0089

GERP RS

5.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

Varity_R

0.22

gMVP

0.33

Mutation Taster

=98/2

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