NM_182914.3:c.-51-11231G>A

Variant names:

• chr14-63897867-G-A
• rs11158519
• NM_182914.3:c.-51-11231G>A

Variant summary

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

The NM_182914.3(SYNE2):​c.-51-11231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,166 control chromosomes in the GnomAD database, including 1,424 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 0.14 (1424 hom., cov: 32)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3	c.-51-11231G>A		intron_variant	Intron 1 of 115	ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6	c.-51-11231G>A		intron_variant	Intron 1 of 115	1	NM_182914.3	ENSP00000450831.2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20683 AN: 152048 Hom.: 1425 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.136 AC: 20690 AN: 152166 Hom.: 1424 Cov.: 32 AF XY: 0.134 AC XY: 9937 AN XY: 74372

African (AFR) AF: 0.144 AC: 5967 AN: 41530

American (AMR) AF: 0.163 AC: 2498 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3470

East Asian (EAS) AF: 0.117 AC: 604 AN: 5172

South Asian (SAS) AF: 0.104 AC: 498 AN: 4810

European-Finnish (FIN) AF: 0.107 AC: 1135 AN: 10580

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 9007 AN: 68002

Other (OTH) AF: 0.126 AC: 267 AN: 2114

Alfa AF: 0.0985 Hom.: 245

Bravo AF: 0.144

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.93
PhyloP100		0.033
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: rs11158519; hg19: chr14-64364585;