NM_182914.3:c.20516+90C>T

Variant names:

• chr14-64225135-C-T
• rs12434245
• NM_182914.3:c.20516+90C>T

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.20516+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,564,992 control chromosomes in the GnomAD database, including 4,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (327 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4607 hom.)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.435

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]

ESR2 (HGNC:3468): (estrogen receptor 2) This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 14-64225135-C-T is Benign according to our data. Variant chr14-64225135-C-T is described in ClinVar as [Benign]. Clinvar id is 1295983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3	c.20516+90C>T		intron_variant	Intron 115 of 115	ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6	c.20516+90C>T		intron_variant	Intron 115 of 115	1	NM_182914.3	ENSP00000450831.2

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8502 AN: 152004 Hom.: 326 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0596

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0757 AC: 106903 AN: 1412870 Hom.: 4607 Cov.: 24 AF XY: 0.0743 AC XY: 52247 AN XY: 703602

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.0878

Gnomad4 ASJ exome AF: 0.0588

Gnomad4 EAS exome AF: 0.00803

Gnomad4 SAS exome AF: 0.0292

Gnomad4 FIN exome AF: 0.0907

Gnomad4 NFE exome AF: 0.0839

Gnomad4 OTH exome AF: 0.0631

GnomAD4 genome AF: 0.0559 AC: 8509 AN: 152122 Hom.: 327 Cov.: 32 AF XY: 0.0552 AC XY: 4101 AN XY: 74360

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0598

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.0929

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0400 Hom.: 40

Bravo AF: 0.0542

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.63

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: rs12434245; hg19: chr14-64691853;