rs1255912

Positions:

• chr14-63995289-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182914.3(SYNE2):​c.2940+87A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,239,140 control chromosomes in the GnomAD database, including 133,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21637 hom., cov: 32)
  • Exomes 𝑓: 0.45 (111910 hom.)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.402

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-63995289-A-C is Benign according to our data. Variant chr14-63995289-A-C is described in ClinVar as [Benign]. Clinvar id is 1246447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE2	NM_182914.3	c.2940+87A>C		intron_variant		ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6	c.2940+87A>C		intron_variant		1	NM_182914.3	ENSP00000450831	P4

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79066 AN: 151854 Hom.: 21618 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.451 AC: 489903 AN: 1087168 Hom.: 111910 AF XY: 0.448 AC XY: 247793 AN XY: 552650

Gnomad4 AFR exome AF: 0.711

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.493

Gnomad4 EAS exome AF: 0.551

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.416

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.521 AC: 79138 AN: 151972 Hom.: 21637 Cov.: 32 AF XY: 0.515 AC XY: 38274 AN XY: 74274

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.499

Alfa AF: 0.480 Hom.: 2242

Bravo AF: 0.537

Asia WGS AF: 0.503 AC: 1746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.41

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: rs1255912; hg19: chr14-64462007;