rs150363140

Variant names:

• chr14-64214385-C-G
• rs150363140
• NM_182914.3:c.19248C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-64214385-C-G
• chr14-64214385-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_182914.3(SYNE2):​c.19248C>G​(p.Pro6416Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,614,114 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: SYNE2 NM_182914.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.46
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 14-64214385-C-G is Benign according to our data. Variant chr14-64214385-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 283702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.46 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00116 (177/152224) while in subpopulation AMR AF = 0.0017 (26/15292). AF 95% confidence interval is 0.00126. There are 0 homozygotes in GnomAd4. There are 92 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 177 AD,Unknown gene.

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.19248C>G	p.Pro6416Pro	synonymous	Exon 106 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.19248C>G	p.Pro6416Pro	synonymous	Exon 106 of 115	NP_055995.4
	SYNE2	NM_182913.4		c.150C>G	p.Pro50Pro	synonymous	Exon 1 of 11	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.19248C>G	p.Pro6416Pro	synonymous	Exon 106 of 116	ENSP00000450831.2	Q8WXH0-2
	SYNE2	ENST00000344113.8	TSL:1	c.19248C>G	p.Pro6416Pro	synonymous	Exon 106 of 115	ENSP00000341781.4	Q8WXH0-1
	SYNE2	ENST00000458046.6	TSL:1	c.150C>G	p.Pro50Pro	synonymous	Exon 1 of 11	ENSP00000391937.2	Q8WXH0-5

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 177 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00117 AC: 294 AN: 250930 AF XY: 0.00106

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00296

Gnomad NFE exome AF: 0.00161

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00117 AC: 1714 AN: 1461890 Hom.: 3 Cov.: 38 AF XY: 0.00113 AC XY: 822 AN XY: 727246

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.000827 AC: 37 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86258

European-Finnish (FIN) AF: 0.00298 AC: 159 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00128 AC: 1422 AN: 1112012

Other (OTH) AF: 0.00103 AC: 62 AN: 60396

GnomAD4 genome AF: 0.00116 AC: 177 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.00124 AC XY: 92 AN XY: 74426

African (AFR) AF: 0.000265 AC: 11 AN: 41532

American (AMR) AF: 0.00170 AC: 26 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00150 AC: 102 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00134 Hom.: 0

Bravo AF: 0.00124

EpiCase AF: 0.00142

EpiControl AF: 0.00107

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Emery-Dreifuss muscular dystrophy 5, autosomal dominant (4)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.075
DANN	Benign	0.77
PhyloP100		-2.5
PromoterAI		0.020	Neutral
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs150363140; hg19: chr14-64681103;