14-64026647-C-T

Variant names:

• chr14-64026647-C-T
• rs143410137
• NM_182914.3:c.6321C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182914.3(SYNE2):​c.6321C>T​(p.Ser2107Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,613,340 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (21 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (136 hom.)
• Consequence: SYNE2 NM_182914.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0860
• Publications: 3 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]

SYNE2 Gene-Disease associations (from GenCC):

• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Emery-Dreifuss muscular dystrophy 5, autosomal dominant

  Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• left ventricular noncompaction

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 14-64026647-C-T is Benign according to our data. Variant chr14-64026647-C-T is described in ClinVar as Benign. ClinVar VariationId is 130502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.086 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0653 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.6321C>T	p.Ser2107Ser	synonymous	Exon 42 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.6321C>T	p.Ser2107Ser	synonymous	Exon 42 of 115	NP_055995.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.6321C>T	p.Ser2107Ser	synonymous	Exon 42 of 116	ENSP00000450831.2	Q8WXH0-2
	SYNE2	ENST00000344113.8	TSL:1	c.6321C>T	p.Ser2107Ser	synonymous	Exon 42 of 115	ENSP00000341781.4	Q8WXH0-1
	SYNE2	ENST00000358025.7	TSL:5	c.6321C>T	p.Ser2107Ser	synonymous	Exon 42 of 116	ENSP00000350719.3	Q8WXH0-2

Frequencies

GnomAD3 genomes AF: 0.00456 AC: 694 AN: 152148 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00693

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.0105 AC: 2615 AN: 248372 AF XY: 0.00770

Gnomad AFR exome AF: 0.000648

Gnomad AMR exome AF: 0.0696

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00792

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00663

GnomAD4 exome AF: 0.00260 AC: 3795 AN: 1461074 Hom.: 136 Cov.: 31 AF XY: 0.00219 AC XY: 1595 AN XY: 726794

African (AFR) AF: 0.000299 AC: 10 AN: 33462

American (AMR) AF: 0.0674 AC: 3005 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26128

East Asian (EAS) AF: 0.0125 AC: 494 AN: 39670

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86138

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53392

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5740

European-Non Finnish (NFE) AF: 0.000112 AC: 125 AN: 1111570

Other (OTH) AF: 0.00202 AC: 122 AN: 60360

GnomAD4 genome AF: 0.00457 AC: 696 AN: 152266 Hom.: 21 Cov.: 33 AF XY: 0.00514 AC XY: 383 AN XY: 74458

African (AFR) AF: 0.000409 AC: 17 AN: 41550

American (AMR) AF: 0.0398 AC: 609 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00714 AC: 37 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68014

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.00175 Hom.: 4

Bravo AF: 0.00829

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.1
DANN	Benign	0.20
PhyloP100		-0.086
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=298/2	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: rs143410137; hg19: chr14-64493365;