16-29873586-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001243332.2(SEZ6L2):c.2248C>T(p.Arg750Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
SEZ6L2
NM_001243332.2 missense
NM_001243332.2 missense
Scores
12
6
1
Clinical Significance
Conservation
PhyloP100: 5.01
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.785
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SEZ6L2 | NM_001243332.2 | c.2248C>T | p.Arg750Trp | missense_variant | 13/18 | ENST00000617533.5 | NP_001230261.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SEZ6L2 | ENST00000617533.5 | c.2248C>T | p.Arg750Trp | missense_variant | 13/18 | 1 | NM_001243332.2 | ENSP00000481917.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251044Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135762
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727234
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74462
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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 19, 2022 | The c.2248C>T (p.R750W) alteration is located in exon 13 (coding exon 13) of the SEZ6L2 gene. This alteration results from a C to T substitution at nucleotide position 2248, causing the arginine (R) at amino acid position 750 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;.;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
.;.;M;.;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;.
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
1.0
.;D;D;.;.
Vest4
MVP
MPC
1.2
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at