rs17101394

chr14-63765668-G-Achr14-63765668-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000674003.1(SYNE2):c.-305+3682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,940 control chromosomes in the GnomAD database, including 2,223 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 0.17 (2223 hom., cov: 32)
• Consequence: SYNE2 ENST00000674003.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	XM_011536576.3	c.-305+3682G>A		intron_variant
SYNE2	XM_047431152.1	c.-305+3939G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000674003.1	c.-305+3682G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25498 AN: 151822 Hom.: 2217 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.168 AC: 25534 AN: 151940 Hom.: 2223 Cov.: 32 AF XY: 0.167 AC XY: 12384 AN XY: 74272

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.171

Alfa AF: 0.154 Hom.: 1678

Bravo AF: 0.176

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.31
Dann	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17101394; hg19: chr14-64232386;