rs1883206

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_StrongBS1BS2

The NM_015374.3(SUN2):c.656C>T(p.Pro219Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,614,222 control chromosomes in the GnomAD database, including 49 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P219P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0095 ( 27 hom., cov: 33)

Exomes 𝑓: 0.00096 ( 22 hom. )

Consequence

SUN2
NM_015374.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.50

Publications

9 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:

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=0.005178392).

BP6

Variant 22-38748742-G-A is Benign according to our data. Variant chr22-38748742-G-A is described in ClinVar as Benign. ClinVar VariationId is 461691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00949 (1446/152344) while in subpopulation AFR AF = 0.0339 (1408/41572). AF 95% confidence interval is 0.0324. There are 27 homozygotes in GnomAd4. There are 689 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN2	NM_015374.3 link	c.656C>T	p.Pro219Leu	missense_variant	Exon 7 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.656C>T	p.Pro219Leu	missense_variant	Exon 7 of 18		NM_015374.3	ENSP00000508608.1		Q9UH99-1

Frequencies

GnomAD3 genomes

AF:

0.00947

AC:

1441

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00252

AC:

633

AN:

251386

AF XY:

0.00184

show subpopulations

Gnomad AFR exome

AF:

0.0358

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000962

AC:

1407

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

618

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0358

AC:

1199

AN:

33480

American (AMR)

AF:

0.00105

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1112006

Other (OTH)

AF:

0.00202

AC:

122

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

165

248

330

413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.00949

AC:

1446

AN:

152344

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

689

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0339

AC:

1408

AN:

41572

American (AMR)

AF:

0.00176

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

142

214

285

356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00376

Hom.:

Bravo

AF:

0.0109

ESP6500AA

AF:

0.0374

AC:

165

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00313

AC:

380

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.42

T;.;T;.;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.73

.;T;T;T;T

MetaRNN

Benign

0.0052

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

N;.;N;.;.

PhyloP100

3.5

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.9

D;D;D;D;.

REVEL

Benign

0.17

Sift

Benign

1.0

T;T;T;T;.

Sift4G

Benign

1.0

T;T;T;T;.

Polyphen

0.0

B;.;B;.;.

Vest4

0.15

MVP

0.26

MPC

0.24

ClinPred

0.019

GERP RS

3.6

Varity_R

0.030

gMVP

0.32

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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