Variant 16-29877442-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001243332.2(SEZ6L2):c.1738C>G(p.Leu580Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,452,004 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SEZ6L2
NM_001243332.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Variant links:

Genes affected

SEZ6L2 (HGNC:30844): (seizure related 6 homolog like 2) This gene encodes a seizure-related protein that is localized on the cell surface. The gene is located in a region of chromosome 16p11.2 that is thought to contain candidate genes for autism spectrum disorders (ASD), though there is no evidence directly implicating this gene in ASD. Increased expression of this gene has been found in lung cancers, and the protein is therefore considered to be a novel prognostic marker for lung cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

SEZ6L2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40095964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L2	NM_001243332.2 linkuse as main transcript	c.1738C>G	p.Leu580Val	missense_variant	11/18	ENST00000617533.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L2	ENST00000617533.5 linkuse as main transcript	c.1738C>G	p.Leu580Val	missense_variant	11/18	1	NM_001243332.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000841

AC:

AN:

237828

Hom.:

AF XY:

0.00000772

AC XY:

AN XY:

129498

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:

0.0000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1452004

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

721948

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000145

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.1738C>G (p.L580V) alteration is located in exon 11 (coding exon 11) of the SEZ6L2 gene. This alteration results from a C to G substitution at nucleotide position 1738, causing the leucine (L) at amino acid position 580 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;.;T;.;.

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.40

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;.;L;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.8

N;N;N;N;.

REVEL

Benign

0.20

Sift

Benign

0.24

T;T;D;T;.

Sift4G

Benign

0.22

T;T;T;T;T

Polyphen

1.0

.;D;D;.;.

Vest4

0.61

MutPred

0.49

.;.;Loss of disorder (P = 0.2229);.;Loss of disorder (P = 0.2229);

MVP

0.59

MPC

0.93

ClinPred

0.59

GERP RS

0.89

Varity_R

0.17

gMVP

0.60

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over