chr14-63868868-G-A

Variant names:

• chr14-63868868-G-A
• rs1959033
• NM_182914.3:c.-52+15725G>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.-52+15725G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 152,188 control chromosomes in the GnomAD database, including 259 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 0.056 (259 hom., cov: 31)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 3 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0669 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.-52+15725G>A		intron	N/A	NP_878918.2
	SYNE2	NM_015180.6		c.-52+15725G>A		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.-52+15725G>A		intron	N/A	ENSP00000450831.2
	SYNE2	ENST00000344113.8	TSL:1	c.-52+15725G>A		intron	N/A	ENSP00000341781.4
	SYNE2	ENST00000341472.9	TSL:1	c.-52+15725G>A		intron	N/A	ENSP00000344528.5

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8481 AN: 152070 Hom.: 260 Cov.: 31

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0566

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0622

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

GnomAD4 genome AF: 0.0557 AC: 8477 AN: 152188 Hom.: 259 Cov.: 31 AF XY: 0.0572 AC XY: 4258 AN XY: 74400

African (AFR) AF: 0.0404 AC: 1677 AN: 41532

American (AMR) AF: 0.0565 AC: 864 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3468

East Asian (EAS) AF: 0.0730 AC: 378 AN: 5180

South Asian (SAS) AF: 0.0649 AC: 313 AN: 4820

European-Finnish (FIN) AF: 0.0640 AC: 677 AN: 10586

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0582 AC: 3959 AN: 67998

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.0608 Hom.: 183

Bravo AF: 0.0560

Asia WGS AF: 0.0540 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.6
DANN	Benign	0.78
PhyloP100		-0.44
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: rs1959033; hg19: chr14-64335586;