rs376340507

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015374.3(SUN2):c.1258G>A(p.Gly420Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,578,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

SUN2
NM_015374.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0890

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049504936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015374.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUN2	NM_015374.3	MANE Select	c.1258G>A	p.Gly420Ser	missense	Exon 12 of 18	NP_056189.1	Q9UH99-1
SUN2	NM_001394427.1		c.1351G>A	p.Gly451Ser	missense	Exon 13 of 19	NP_001381356.1
SUN2	NM_001199579.2		c.1321G>A	p.Gly441Ser	missense	Exon 12 of 18	NP_001186508.1	Q9UH99-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUN2	ENST00000689035.1	MANE Select	c.1258G>A	p.Gly420Ser	missense	Exon 12 of 18	ENSP00000508608.1	Q9UH99-1
SUN2	ENST00000405018.5	TSL:1	c.1321G>A	p.Gly441Ser	missense	Exon 12 of 18	ENSP00000385616.1	Q9UH99-2
SUN2	ENST00000405510.5	TSL:1	c.1258G>A	p.Gly420Ser	missense	Exon 13 of 19	ENSP00000385740.1	Q9UH99-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000426

AC:

AN:

187810

AF XY:

0.0000294

show subpopulations

Gnomad AFR exome

AF:

0.000379

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:

0.0000254

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1426450

Hom.:

Cov.:

AF XY:

0.0000326

AC XY:

AN XY:

706450

show subpopulations

African (AFR)

AF:

0.000213

AC:

AN:

32880

American (AMR)

AF:

0.00

AC:

AN:

39796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25402

East Asian (EAS)

AF:

0.0000788

AC:

AN:

38082

South Asian (SAS)

AF:

0.0000734

AC:

AN:

81788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

0.0000238

AC:

AN:

1094182

Other (OTH)

AF:

0.0000848

AC:

AN:

58966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000151

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

41448

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68020

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000123

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000458

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000167

AC:

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Emery-Dreifuss muscular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.8

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.019

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.51

M_CAP

Benign

0.0090

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.42

PhyloP100

0.089

PrimateAI

Benign

0.33

PROVEAN

Benign

0.020

REVEL

Benign

0.043

Sift

Benign

0.46

Sift4G

Benign

0.77

Polyphen

0.018

Vest4

0.14

MVP

0.095

MPC

0.24

ClinPred

0.020

GERP RS

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.21

Mutation Taster

=95/5

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over