Variant rs375543783 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_182914.3(SYNE2):c.6685C>A(p.Leu2229Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L2229V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.32

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21105376).

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000527 (77/1461800) while in subpopulation NFE AF= 0.0000665 (74/1111964). AF 95% confidence interval is 0.0000542. There are 0 homozygotes in gnomad4_exome. There are 39 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	NM_182914.3 linkuse as main transcript	c.6685C>A	p.Leu2229Ile	missense_variant	43/116	ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6 linkuse as main transcript	c.6685C>A	p.Leu2229Ile	missense_variant	43/116	1	NM_182914.3	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248824

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135146

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000527

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000665

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

T;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

M;.;M;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.28

T;D;T;T

Sift4G

Benign

0.066

T;T;T;T

Polyphen

1.0

D;.;D;.

Vest4

0.28

MutPred

0.36

Loss of ubiquitination at K2227 (P = 0.0638);Loss of ubiquitination at K2227 (P = 0.0638);Loss of ubiquitination at K2227 (P = 0.0638);Loss of ubiquitination at K2227 (P = 0.0638);

MVP

0.66

MPC

0.33

ClinPred

0.90

GERP RS

5.5

Varity_R

0.11

gMVP

0.034

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over