rs79037871

Variant names:

• chr14-63983805-A-G
• rs79037871
• NM_182914.3:c.2070A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-63983805-A-G
• chr14-63983805-A-C
• chr14-63983805-A-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.2070A>G​(p.Leu690Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,611,738 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (12 hom.)
• Consequence: SYNE2 NM_182914.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.612
• 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
• 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=-0.88).
• BP6: Variant 14-63983805-A-G is Benign according to our data. Variant chr14-63983805-A-G is described in ClinVar as Benign. ClinVar VariationId is 130492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.612 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00171 (260/152352) while in subpopulation AMR AF = 0.012 (184/15302). AF 95% confidence interval is 0.0106. There are 4 homozygotes in GnomAd4. There are 164 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 260 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.2070A>G	p.Leu690Leu	synonymous	Exon 18 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.2070A>G	p.Leu690Leu	synonymous	Exon 18 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.2070A>G	p.Leu690Leu	synonymous	Exon 18 of 116	ENSP00000450831.2	Q8WXH0-2
	SYNE2	ENST00000344113.8	TSL:1	c.2070A>G	p.Leu690Leu	synonymous	Exon 18 of 115	ENSP00000341781.4	Q8WXH0-1
	SYNE2	ENST00000358025.7	TSL:5	c.2070A>G	p.Leu690Leu	synonymous	Exon 18 of 116	ENSP00000350719.3	Q8WXH0-2

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 259 AN: 152234 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00922

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00367 AC: 914 AN: 248880 AF XY: 0.00297

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.0213

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000886

Gnomad OTH exome AF: 0.00315

GnomAD4 exome AF: 0.000989 AC: 1443 AN: 1459386 Hom.: 12 Cov.: 29 AF XY: 0.000936 AC XY: 680 AN XY: 726142

African (AFR) AF: 0.000120 AC: 4 AN: 33426

American (AMR) AF: 0.0195 AC: 872 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00222 AC: 58 AN: 26094

East Asian (EAS) AF: 0.00629 AC: 249 AN: 39558

South Asian (SAS) AF: 0.000685 AC: 59 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.000113 AC: 125 AN: 1110070

Other (OTH) AF: 0.00123 AC: 74 AN: 60288

GnomAD4 genome AF: 0.00171 AC: 260 AN: 152352 Hom.: 4 Cov.: 32 AF XY: 0.00220 AC XY: 164 AN XY: 74496

African (AFR) AF: 0.000168 AC: 7 AN: 41586

American (AMR) AF: 0.0120 AC: 184 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00924 AC: 48 AN: 5192

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68038

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000511 Hom.: 0

Bravo AF: 0.00305

Asia WGS AF: 0.00376 AC: 13 AN: 3476

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Emery-Dreifuss muscular dystrophy 5, autosomal dominant (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.39
PhyloP100		-0.61
Mutation Taster		=290/10	polymorphism

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: rs79037871; hg19: chr14-64450523;