ENST00000674003.1:c.-52+218C>T

Variant names:

• chr14-63852971-C-T
• rs143315154
• ENST00000674003.1:c.-52+218C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The ENST00000674003.1(SYNE2):​c.-52+218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 151,768 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (43 hom., cov: 32)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: SYNE2 ENST00000674003.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.186
• Publications: 4 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

ENSG00000306681 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 14-63852971-C-T is Benign according to our data. Variant chr14-63852971-C-T is described in ClinVar as Benign. ClinVar VariationId is 313475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0209 (3164/151390) while in subpopulation AMR AF = 0.0337 (513/15220). AF 95% confidence interval is 0.0313. There are 43 homozygotes in GnomAd4. There are 1574 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3164 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674003.1. 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.-224C>T		upstream_gene	N/A	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.-224C>T		upstream_gene	N/A	NP_055995.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	ENST00000674003.1		c.-52+218C>T		intron	N/A	ENSP00000501132.1	A0A669KB61
	SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.-224C>T		upstream_gene	N/A	ENSP00000450831.2	Q8WXH0-2
	SYNE2	ENST00000344113.8	TSL:1	c.-224C>T		upstream_gene	N/A	ENSP00000341781.4	Q8WXH0-1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3150 AN: 151280 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00908

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.0344

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.00540

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0303

GnomAD4 exome AF: 0.0556 AC: 21 AN: 378 Hom.: 0 Cov.: 0 AF XY: 0.0647 AC XY: 18 AN XY: 278

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 12

South Asian (SAS) AF: 0.0469 AC: 3 AN: 64

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0536 AC: 15 AN: 280

Other (OTH) AF: 0.200 AC: 2 AN: 10

GnomAD4 genome AF: 0.0209 AC: 3164 AN: 151390 Hom.: 43 Cov.: 32 AF XY: 0.0213 AC XY: 1574 AN XY: 73990

African (AFR) AF: 0.00940 AC: 389 AN: 41400

American (AMR) AF: 0.0337 AC: 513 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0344 AC: 119 AN: 3464

East Asian (EAS) AF: 0.000587 AC: 3 AN: 5114

South Asian (SAS) AF: 0.0332 AC: 160 AN: 4818

European-Finnish (FIN) AF: 0.00540 AC: 56 AN: 10364

Middle Eastern (MID) AF: 0.0310 AC: 9 AN: 290

European-Non Finnish (NFE) AF: 0.0271 AC: 1832 AN: 67710

Other (OTH) AF: 0.0310 AC: 65 AN: 2098

Alfa AF: 0.0228 Hom.: 7

Bravo AF: 0.0207

Asia WGS AF: 0.0240 AC: 81 AN: 3348

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	-0.28
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		0.19
PromoterAI		0.11	Neutral
Mutation Taster		=297/3	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143315154; hg19: chr14-64319689;