rs2072799
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_015374.3(SUN2):c.97A>G(p.Thr33Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00608 in 1,613,768 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0079 ( 86 hom., cov: 33)
Exomes 𝑓: 0.0059 ( 599 hom. )
Consequence
SUN2
NM_015374.3 missense
NM_015374.3 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: -0.170
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0013588965).
BP6
?
Variant 22-38752532-T-C is Benign according to our data. Variant chr22-38752532-T-C is described in ClinVar as [Benign]. Clinvar id is 461693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUN2 | NM_015374.3 | c.97A>G | p.Thr33Ala | missense_variant | 2/18 | ENST00000689035.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUN2 | ENST00000689035.1 | c.97A>G | p.Thr33Ala | missense_variant | 2/18 | NM_015374.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00791 AC: 1204AN: 152212Hom.: 85 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0150 AC: 3748AN: 249948Hom.: 315 AF XY: 0.0140 AC XY: 1894AN XY: 135240
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GnomAD4 exome AF: 0.00589 AC: 8607AN: 1461438Hom.: 599 Cov.: 32 AF XY: 0.00574 AC XY: 4176AN XY: 727010
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GnomAD4 genome ? AF: 0.00790 AC: 1204AN: 152330Hom.: 86 Cov.: 33 AF XY: 0.00885 AC XY: 659AN XY: 74490
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ExAC
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Asia WGS
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3478
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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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;T;.;.;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;.;.;.;.;.;.;.
MutationTaster
Benign
P;P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;D;D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T;T;D;T;T;D;T
Sift4G
Benign
T;T;T;T;.;.;.;T;.;.
Polyphen
B;.;B;.;.;.;.;.;.;.
Vest4
MPC
0.23
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at