rs149391344

Variant names:

• chr14-64081475-T-C
• rs149391344
• NM_182914.3:c.11379T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-64081475-T-C
• chr14-64081475-T-G

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.11379T>C​(p.Leu3793Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,614,176 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (18 hom.)
• Consequence: SYNE2 NM_182914.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.290
• 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]

SYNE2 Gene-Disease associations (from GenCC):

• autosomal dominant Emery-Dreifuss muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Emery-Dreifuss muscular dystrophy 5, autosomal dominant

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-64081475-T-C is Benign according to our data. Variant chr14-64081475-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 282477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.29 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00313 (476/152296) while in subpopulation NFE AF = 0.00466 (317/68024). AF 95% confidence interval is 0.00424. There are 6 homozygotes in GnomAd4. There are 219 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 476 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.11379T>C	p.Leu3793Leu	synonymous	Exon 57 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.11379T>C	p.Leu3793Leu	synonymous	Exon 57 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.11379T>C	p.Leu3793Leu	synonymous	Exon 57 of 116	ENSP00000450831.2	Q8WXH0-2
	SYNE2	ENST00000344113.8	TSL:1	c.11379T>C	p.Leu3793Leu	synonymous	Exon 57 of 115	ENSP00000341781.4	Q8WXH0-1
	SYNE2	ENST00000394768.6	TSL:1	n.843T>C		non_coding_transcript_exon	Exon 4 of 63

Frequencies

GnomAD3 genomes AF: 0.00313 AC: 477 AN: 152178 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00466

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00356 AC: 895 AN: 251464 AF XY: 0.00326

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00304

Gnomad ASJ exome AF: 0.00833

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00721

Gnomad NFE exome AF: 0.00404

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00411 AC: 6010 AN: 1461880 Hom.: 18 Cov.: 32 AF XY: 0.00404 AC XY: 2939 AN XY: 727236

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.00309 AC: 138 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00754 AC: 197 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00152 AC: 131 AN: 86258

European-Finnish (FIN) AF: 0.00786 AC: 420 AN: 53418

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5766

European-Non Finnish (NFE) AF: 0.00431 AC: 4790 AN: 1112004

Other (OTH) AF: 0.00422 AC: 255 AN: 60394

GnomAD4 genome AF: 0.00313 AC: 476 AN: 152296 Hom.: 6 Cov.: 32 AF XY: 0.00294 AC XY: 219 AN XY: 74474

African (AFR) AF: 0.000625 AC: 26 AN: 41568

American (AMR) AF: 0.00190 AC: 29 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4822

European-Finnish (FIN) AF: 0.00612 AC: 65 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00466 AC: 317 AN: 68024

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.00422 Hom.: 1

Bravo AF: 0.00268

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00403

EpiControl AF: 0.00468

ClinVar

ClinVar submissions

Significance: Benign/Likely 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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.64
PhyloP100		0.29
Mutation Taster		=100/0	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: rs149391344; hg19: chr14-64548193;