rs12889954

Variant names:

• chr14-63920750-T-C
• rs12889954
• NM_182914.3:c.79+11523T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-63920750-T-C
• chr14-63920750-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182914.3(SYNE2):​c.79+11523T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,280 control chromosomes in the GnomAD database, including 5,215 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5215 hom., cov: 29)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 6 publications found

Genes affected

SYNE2 (HGNC:17084): (spectrin repeat containing nuclear envelope protein 2) The protein encoded by this gene is a nuclear outer membrane protein that binds cytoplasmic F-actin. This binding tethers the nucleus to the cytoskeleton and aids in the maintenance of the structural integrity of the nucleus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

SYNE2 Gene-Disease associations (from GenCC):

• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Emery-Dreifuss muscular dystrophy 5, autosomal dominant

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• left ventricular noncompaction

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182914.3. 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
	SYNE2	NM_182914.3	MANE Select	c.79+11523T>C		intron	N/A	NP_878918.2
	SYNE2	NM_015180.6		c.79+11523T>C		intron	N/A	NP_055995.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.79+11523T>C		intron	N/A	ENSP00000450831.2
	SYNE2	ENST00000344113.8	TSL:1	c.79+11523T>C		intron	N/A	ENSP00000341781.4
	SYNE2	ENST00000341472.9	TSL:1	c.79+11523T>C		intron	N/A	ENSP00000344528.5

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35427 AN: 151162 Hom.: 5208 Cov.: 29

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.234 AC: 35463 AN: 151280 Hom.: 5215 Cov.: 29 AF XY: 0.232 AC XY: 17139 AN XY: 73868

African (AFR) AF: 0.422 AC: 17357 AN: 41148

American (AMR) AF: 0.219 AC: 3329 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3464

East Asian (EAS) AF: 0.143 AC: 726 AN: 5092

South Asian (SAS) AF: 0.230 AC: 1097 AN: 4760

European-Finnish (FIN) AF: 0.119 AC: 1242 AN: 10480

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10306 AN: 67838

Other (OTH) AF: 0.214 AC: 450 AN: 2098

Alfa AF: 0.202 Hom.: 6338

Bravo AF: 0.251

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.77
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs12889954; hg19: chr14-64387468;