rs371327530

Variant names:

• chr14-64002788-A-T
• rs371327530
• NM_182914.3:c.3855A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-64002788-A-T
• chr14-64002788-A-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.3855A>T​(p.Val1285Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000038 in 1,605,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: SYNE2 NM_182914.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0240
• Publications: 0 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=-0.86).
• BP6: Variant 14-64002788-A-T is Benign according to our data. Variant chr14-64002788-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 538373.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.024 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000278 (4/143992) while in subpopulation NFE AF = 0.0000464 (3/64604). AF 95% confidence interval is 0.0000123. There are 0 homozygotes in GnomAd4. There are 0 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 57 Unknown,AD 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.3855A>T	p.Val1285Val	synonymous	Exon 30 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.3855A>T	p.Val1285Val	synonymous	Exon 30 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.3855A>T	p.Val1285Val	synonymous	Exon 30 of 116	ENSP00000450831.2	Q8WXH0-2
	SYNE2	ENST00000344113.8	TSL:1	c.3855A>T	p.Val1285Val	synonymous	Exon 30 of 115	ENSP00000341781.4	Q8WXH0-1
	SYNE2	ENST00000358025.7	TSL:5	c.3855A>T	p.Val1285Val	synonymous	Exon 30 of 116	ENSP00000350719.3	Q8WXH0-2

Frequencies

GnomAD3 genomes AF: 0.0000278 AC: 4 AN: 143992 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000464

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 5 AN: 248968 AF XY: 0.0000370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461616 Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23 AN XY: 727068

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111864

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome AF: 0.0000278 AC: 4 AN: 143992 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 70628

African (AFR) AF: 0.0000258 AC: 1 AN: 38690

American (AMR) AF: 0.00 AC: 0 AN: 14686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3318

East Asian (EAS) AF: 0.00 AC: 0 AN: 4748

South Asian (SAS) AF: 0.00 AC: 0 AN: 4544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000464 AC: 3 AN: 64604

Other (OTH) AF: 0.00 AC: 0 AN: 1932

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.33
DANN	Benign	0.36
PhyloP100		-0.024

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: rs371327530; hg19: chr14-64469506; COSMIC: COSV59954757; COSMIC: COSV59954757;