14-63763371-T-C

Variant names:

• chr14-63763371-T-C
• rs4902242
• ENST00000674003.1:c.-305+1385T>C

Variant summary

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

The ENST00000674003.1(SYNE2):​c.-305+1385T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,102 control chromosomes in the GnomAD database, including 1,100 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 0.12 (1100 hom., cov: 32)
• Consequence: SYNE2 ENST00000674003.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	XM_011536576.3	c.-305+1385T>C		intron_variant	Intron 1 of 116		XP_011534878.1
SYNE2	XM_047431152.1	c.-305+1642T>C		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+1385T>C		intron_variant	Intron 1 of 23			ENSP00000501132.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18142 AN: 151984 Hom.: 1099 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0978

Gnomad FIN AF: 0.0955

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.119 AC: 18162 AN: 152102 Hom.: 1100 Cov.: 32 AF XY: 0.118 AC XY: 8766 AN XY: 74350

African (AFR) AF: 0.108 AC: 4476 AN: 41498

American (AMR) AF: 0.157 AC: 2398 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 575 AN: 3472

East Asian (EAS) AF: 0.115 AC: 597 AN: 5180

South Asian (SAS) AF: 0.0974 AC: 470 AN: 4824

European-Finnish (FIN) AF: 0.0955 AC: 1010 AN: 10574

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8255 AN: 67986

Other (OTH) AF: 0.119 AC: 251 AN: 2110

Alfa AF: 0.122 Hom.: 2389

Bravo AF: 0.126

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.44
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs4902242; hg19: chr14-64230089;