rs137966643

Variant names:

• chr22-38751330-C-A
• NM_015374.3:c.166G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-38751330-C-A
• chr22-38751330-C-G
• chr22-38751330-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015374.3(SUN2):​c.166G>T​(p.Ala56Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUN2 NM_015374.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06308478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN2	NM_015374.3	c.166G>T	p.Ala56Ser	missense_variant	Exon 3 of 18	ENST00000689035.1	NP_056189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN2	ENST00000689035.1	c.166G>T	p.Ala56Ser	missense_variant	Exon 3 of 18		NM_015374.3	ENSP00000508608.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T;.;T;.;.;.;.;.;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.70	.;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.063	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M;M;.;.;.;.;.;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.25	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.073
Sift	Benign	0.23	T;T;T;D;D;D;D;D;D;D
Sift4G	Benign	0.26	T;T;T;T;.;.;.;T;.;.
Polyphen		0.19	B;.;B;.;.;.;.;.;.;.
Vest4		0.20
MutPred		0.11		Gain of phosphorylation at A56 (P = 0.0112);Gain of phosphorylation at A56 (P = 0.0112);Gain of phosphorylation at A56 (P = 0.0112);Gain of phosphorylation at A56 (P = 0.0112);Gain of phosphorylation at A56 (P = 0.0112);Gain of phosphorylation at A56 (P = 0.0112);Gain of phosphorylation at A56 (P = 0.0112);Gain of phosphorylation at A56 (P = 0.0112);Gain of phosphorylation at A56 (P = 0.0112);Gain of phosphorylation at A56 (P = 0.0112);
MVP		0.41
MPC		0.46
ClinPred		0.48	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-39147335;