rs150014549

chr22-38738981-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_015374.3(SUN2):c.1671C>T(p.Ser557=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,609,562 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000098 (1 hom.)
• Consequence: SUN2 NM_015374.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.201

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 22-38738981-G-A is Benign according to our data. Variant chr22-38738981-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 530838.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.201 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN2	NM_015374.3	c.1671C>T	p.Ser557=	synonymous_variant	15/18	ENST00000689035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN2	ENST00000689035.1	c.1671C>T	p.Ser557=	synonymous_variant	15/18		NM_015374.3	P2
	ENST00000418803.1	n.518G>A		non_coding_transcript_exon_variant	3/3	5
	ENST00000416406.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152172 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000238 AC: 57 AN: 239172 Hom.: 1 AF XY: 0.000216 AC XY: 28 AN XY: 129674

Gnomad AFR exome AF: 0.000403

Gnomad AMR exome AF: 0.000509

Gnomad ASJ exome AF: 0.000925

Gnomad EAS exome AF: 0.0000567

Gnomad SAS exome AF: 0.000646

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000465

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000981 AC: 143 AN: 1457272 Hom.: 1 Cov.: 33 AF XY: 0.000104 AC XY: 75 AN XY: 724582

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000455

Gnomad4 ASJ exome AF: 0.000616

Gnomad4 EAS exome AF: 0.0000760

Gnomad4 SAS exome AF: 0.000597

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000306

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152290 Hom.: 1 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74464

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000162

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	12
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs150014549; hg19: chr22-39134986; COSMIC: COSV53302963; COSMIC: COSV53302963;