rs11158519

Positions:

• chr14-63897867-G-A
• chr14-63897867-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• 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/exons	MANE	UniProt
SYNE2	NM_182914.3	c.-51-11231G>A		intron_variant		ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6	c.-51-11231G>A		intron_variant		1	NM_182914.3	P4

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0980 Hom.: 243

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11158519; hg19: chr14-64364585;