Genetic Variant SUN2:p.Arg10Gly (chr22-38752601-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015374.3(SUN2):c.28C>G(p.Arg10Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R10H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SUN2
NM_015374.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.35

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33767363).

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
SUN2	NM_015374.3	MANE Select	c.28C>G	p.Arg10Gly	missense	Exon 2 of 18	NP_056189.1
SUN2	NM_001394427.1		c.28C>G	p.Arg10Gly	missense	Exon 2 of 19	NP_001381356.1
SUN2	NM_001199579.2		c.28C>G	p.Arg10Gly	missense	Exon 2 of 18	NP_001186508.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SUN2	ENST00000689035.1	MANE Select	c.28C>G	p.Arg10Gly	missense	Exon 2 of 18	ENSP00000508608.1
SUN2	ENST00000405018.5	TSL:1	c.28C>G	p.Arg10Gly	missense	Exon 2 of 18	ENSP00000385616.1
SUN2	ENST00000405510.5	TSL:1	c.28C>G	p.Arg10Gly	missense	Exon 3 of 19	ENSP00000385740.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250646

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111950

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.86

M_CAP

Benign

0.019

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.6

PhyloP100

5.3

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.3

REVEL

Benign

0.14

Sift

Benign

0.067

Sift4G

Benign

0.20

Polyphen

1.0

Vest4

0.68

MVP

0.57

MPC

0.99

ClinPred

0.74

GERP RS

4.8

Varity_R

0.11

gMVP

0.23

Mutation Taster

=81/19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over