22-38751220-G-A

Variant names:

• chr22-38751220-G-A
• rs111670814
• NM_015374.3:c.276C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_015374.3(SUN2):​c.276C>T​(p.Asp92Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,612,412 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00067 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: SUN2 NM_015374.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.221
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-38751220-G-A is Benign according to our data. Variant chr22-38751220-G-A is described in ClinVar as Benign. ClinVar VariationId is 461684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.221 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN2	NM_015374.3	MANE Select	c.276C>T	p.Asp92Asp	synonymous	Exon 3 of 18	NP_056189.1
	SUN2	NM_001394427.1		c.276C>T	p.Asp92Asp	synonymous	Exon 3 of 19	NP_001381356.1
	SUN2	NM_001199579.2		c.276C>T	p.Asp92Asp	synonymous	Exon 3 of 18	NP_001186508.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN2	ENST00000689035.1	MANE Select	c.276C>T	p.Asp92Asp	synonymous	Exon 3 of 18	ENSP00000508608.1
	SUN2	ENST00000405018.5	TSL:1	c.276C>T	p.Asp92Asp	synonymous	Exon 3 of 18	ENSP00000385616.1
	SUN2	ENST00000405510.5	TSL:1	c.276C>T	p.Asp92Asp	synonymous	Exon 4 of 19	ENSP00000385740.1

Frequencies

GnomAD3 genomes AF: 0.000637 AC: 97 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00207

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000183 AC: 46 AN: 250772 AF XY: 0.000125

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000137 AC: 200 AN: 1460074 Hom.: 0 Cov.: 32 AF XY: 0.000132 AC XY: 96 AN XY: 726010

African (AFR) AF: 0.00251 AC: 84 AN: 33442

American (AMR) AF: 0.000314 AC: 14 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.000429 AC: 17 AN: 39650

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86234

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53384

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1110624

Other (OTH) AF: 0.000481 AC: 29 AN: 60320

GnomAD4 genome AF: 0.000670 AC: 102 AN: 152338 Hom.: 1 Cov.: 33 AF XY: 0.000658 AC XY: 49 AN XY: 74492

African (AFR) AF: 0.00219 AC: 91 AN: 41590

American (AMR) AF: 0.000327 AC: 5 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000377 Hom.: 0

Bravo AF: 0.000892

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.76
PhyloP100		-0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs111670814; hg19: chr22-39147225;