rs1152588

Variant names:

• chr14-64221457-G-C
• rs1152588
• NM_182914.3:c.20062-119G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-64221457-G-C
• chr14-64221457-G-A
• chr14-64221457-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182914.3(SYNE2):​c.20062-119G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,588,304 control chromosomes in the GnomAD database, including 265,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (34069 hom., cov: 32)
  • Exomes 𝑓: 0.56 (231041 hom.)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.686
• Publications: 13 publications found

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]

ESR2 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
• familial medullary thyroid carcinoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ovarian dysgenesis 8

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 14-64221457-G-C is Benign according to our data. Variant chr14-64221457-G-C is described in ClinVar as Benign. ClinVar VariationId is 281196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182914.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	NM_182914.3	MANE Select	c.20062-119G>C		intron	N/A	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.19993-119G>C		intron	N/A	NP_055995.4
	SYNE2	NM_182913.4		c.964-77G>C		intron	N/A	NP_878917.1	Q8WXH0-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.20062-119G>C		intron	N/A	ENSP00000450831.2	Q8WXH0-2
	SYNE2	ENST00000344113.8	TSL:1	c.19993-119G>C		intron	N/A	ENSP00000341781.4	Q8WXH0-1
	SYNE2	ENST00000458046.6	TSL:1	c.964-77G>C		intron	N/A	ENSP00000391937.2	Q8WXH0-5

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99328 AN: 151980 Hom.: 34017 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.563 AC: 809068 AN: 1436206 Hom.: 231041 AF XY: 0.560 AC XY: 400253 AN XY: 714314

African (AFR) AF: 0.890 AC: 29259 AN: 32878

American (AMR) AF: 0.531 AC: 23437 AN: 44138

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 16443 AN: 25652

East Asian (EAS) AF: 0.650 AC: 25656 AN: 39454

South Asian (SAS) AF: 0.498 AC: 42218 AN: 84762

European-Finnish (FIN) AF: 0.566 AC: 29623 AN: 52338

Middle Eastern (MID) AF: 0.595 AC: 3343 AN: 5622

European-Non Finnish (NFE) AF: 0.553 AC: 604099 AN: 1091960

Other (OTH) AF: 0.589 AC: 34990 AN: 59402

GnomAD4 genome AF: 0.654 AC: 99434 AN: 152098 Hom.: 34069 Cov.: 32 AF XY: 0.650 AC XY: 48311 AN XY: 74326

African (AFR) AF: 0.877 AC: 36430 AN: 41516

American (AMR) AF: 0.558 AC: 8530 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2224 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3630 AN: 5178

South Asian (SAS) AF: 0.500 AC: 2404 AN: 4812

European-Finnish (FIN) AF: 0.577 AC: 6089 AN: 10554

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37924 AN: 67972

Other (OTH) AF: 0.631 AC: 1331 AN: 2108

Alfa AF: 0.605 Hom.: 3445

Bravo AF: 0.666

Asia WGS AF: 0.612 AC: 2127 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Emery-Dreifuss muscular dystrophy 5, autosomal dominant (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.46
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1152588; hg19: chr14-64688175; COSMIC: COSV59952185; COSMIC: COSV59952185;