rs7157785

Variant names:

• chr14-63768838-G-T
• rs7157785
• ENST00000674003.1:c.-305+6852G>T

Variant summary

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

The ENST00000674003.1(SYNE2):​c.-305+6852G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,816 control chromosomes in the GnomAD database, including 4,929 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 (4929 hom., cov: 31)
• Consequence: SYNE2 ENST00000674003.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 32 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	XM_011536576.3	c.-305+6852G>T		intron_variant	Intron 1 of 116		XP_011534878.1
SYNE2	XM_047431152.1	c.-305+7109G>T		intron_variant	Intron 1 of 116		XP_047287108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000674003.1	c.-305+6852G>T		intron_variant	Intron 1 of 23			ENSP00000501132.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34823 AN: 151698 Hom.: 4895 Cov.: 31

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.230 AC: 34904 AN: 151816 Hom.: 4929 Cov.: 31 AF XY: 0.226 AC XY: 16750 AN XY: 74196

African (AFR) AF: 0.398 AC: 16435 AN: 41330

American (AMR) AF: 0.227 AC: 3450 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3464

East Asian (EAS) AF: 0.101 AC: 522 AN: 5180

South Asian (SAS) AF: 0.153 AC: 738 AN: 4824

European-Finnish (FIN) AF: 0.118 AC: 1241 AN: 10560

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11156 AN: 67956

Other (OTH) AF: 0.213 AC: 450 AN: 2108

Alfa AF: 0.183 Hom.: 8734

Bravo AF: 0.247

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.53
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs7157785; hg19: chr14-64235556;