NM_182914.3:c.*386G>C

Variant names:

• chr14-64225912-G-C
• rs1152582
• NM_182914.3:c.*386G>C

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.*386G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 421,840 control chromosomes in the GnomAD database, including 80,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34299 hom., cov: 31)
  • Exomes 𝑓: 0.58 (46110 hom.)
• Consequence: SYNE2 NM_182914.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.766
• Publications: 23 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=-0.89).
• BP6: Variant 14-64225912-G-C is Benign according to our data. Variant chr14-64225912-G-C is described in ClinVar as Benign. ClinVar VariationId is 313681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 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.*386G>C		3_prime_UTR	Exon 116 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.*386G>C		3_prime_UTR	Exon 115 of 115	NP_055995.4
	SYNE2	NM_182913.4		c.*386G>C		3_prime_UTR	Exon 11 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.*386G>C		3_prime_UTR	Exon 116 of 116	ENSP00000450831.2	Q8WXH0-2
	SYNE2	ENST00000344113.8	TSL:1	c.*386G>C		3_prime_UTR	Exon 115 of 115	ENSP00000341781.4	Q8WXH0-1
	SYNE2	ENST00000458046.6	TSL:1	c.*386G>C		3_prime_UTR	Exon 11 of 11	ENSP00000391937.2	Q8WXH0-5

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99718 AN: 151944 Hom.: 34245 Cov.: 31

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.577 AC: 155692 AN: 269778 Hom.: 46110 Cov.: 0 AF XY: 0.573 AC XY: 79017 AN XY: 137916

African (AFR) AF: 0.884 AC: 8433 AN: 9542

American (AMR) AF: 0.543 AC: 5872 AN: 10822

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 5983 AN: 9446

East Asian (EAS) AF: 0.633 AC: 12545 AN: 19808

South Asian (SAS) AF: 0.495 AC: 9961 AN: 20138

European-Finnish (FIN) AF: 0.561 AC: 8615 AN: 15362

Middle Eastern (MID) AF: 0.614 AC: 779 AN: 1268

European-Non Finnish (NFE) AF: 0.561 AC: 93345 AN: 166444

Other (OTH) AF: 0.599 AC: 10159 AN: 16948

GnomAD4 genome AF: 0.656 AC: 99825 AN: 152062 Hom.: 34299 Cov.: 31 AF XY: 0.652 AC XY: 48473 AN XY: 74312

African (AFR) AF: 0.879 AC: 36498 AN: 41516

American (AMR) AF: 0.561 AC: 8569 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2207 AN: 3472

East Asian (EAS) AF: 0.693 AC: 3583 AN: 5168

South Asian (SAS) AF: 0.505 AC: 2424 AN: 4800

European-Finnish (FIN) AF: 0.581 AC: 6129 AN: 10552

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38199 AN: 67950

Other (OTH) AF: 0.637 AC: 1346 AN: 2114

Alfa AF: 0.608 Hom.: 3461

Bravo AF: 0.669

Asia WGS AF: 0.609 AC: 2119 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-0.77
Mutation Taster		=100/0	polymorphism (auto)

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: rs1152582; hg19: chr14-64692630;