chr14-63848602-G-T

Position:

• chr14-63848602-G-T

Variant summary

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

The ENST00000674003.1(SYNE2):​c.-304-3899G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,026 control chromosomes in the GnomAD database, including 15,457 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 0.42 (15457 hom., cov: 32)
• Consequence: SYNE2 ENST00000674003.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	XM_011536576.3	c.-304-3899G>T		intron_variant
SYNE2	XM_047431152.1	c.-304-3899G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000674003.1	c.-304-3899G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64497 AN: 151908 Hom.: 15444 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.424 AC: 64531 AN: 152026 Hom.: 15457 Cov.: 32 AF XY: 0.432 AC XY: 32081 AN XY: 74304

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.458

Alfa AF: 0.479 Hom.: 7607

Bravo AF: 0.399

Asia WGS AF: 0.452 AC: 1577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.6
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11158515; hg19: chr14-64315320;