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GeneBe

rs141051927

chr22-38740321-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015374.3(SUN2):c.1302G>A(p.Ser434=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,602,598 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 10 hom. )

Consequence

SUN2
NM_015374.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.59
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-38740321-C-T is Benign according to our data. Variant chr22-38740321-C-T is described in ClinVar as [Benign]. Clinvar id is 530832.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.59 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SUN2NM_015374.3 linkuse as main transcriptc.1302G>A p.Ser434= synonymous_variant 12/18 ENST00000689035.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SUN2ENST00000689035.1 linkuse as main transcriptc.1302G>A p.Ser434= synonymous_variant 12/18 NM_015374.3 P2Q9UH99-1
ENST00000416406.1 linkuse as main transcriptn.165+1154C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00204
AC:
311
AN:
152176
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0129
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00229
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00198
AC:
445
AN:
224846
Hom.:
4
AF XY:
0.00187
AC XY:
231
AN XY:
123206
show subpopulations
Gnomad AFR exome
AF:
0.000378
Gnomad AMR exome
AF:
0.0000306
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000708
Gnomad FIN exome
AF:
0.0116
Gnomad NFE exome
AF:
0.00210
Gnomad OTH exome
AF:
0.00109
GnomAD4 exome
AF:
0.00202
AC:
2935
AN:
1450422
Hom.:
10
Cov.:
31
AF XY:
0.00194
AC XY:
1397
AN XY:
720780
show subpopulations
Gnomad4 AFR exome
AF:
0.000301
Gnomad4 AMR exome
AF:
0.0000458
Gnomad4 ASJ exome
AF:
0.0000774
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000355
Gnomad4 FIN exome
AF:
0.0123
Gnomad4 NFE exome
AF:
0.00200
Gnomad4 OTH exome
AF:
0.00122
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00204
AC:
311
AN:
152176
Hom.:
2
Cov.:
32
AF XY:
0.00248
AC XY:
184
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.000338
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0129
Gnomad4 NFE
AF:
0.00229
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.00195
Hom.:
0
Bravo
AF:
0.00122

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
0.046
Dann
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141051927; hg19: chr22-39136326; API