16-29894561-T-C

Variant names:

• chr16-29894561-T-C
• rs13332660
• NM_001243332.2:c.853+698A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243332.2(SEZ6L2):​c.853+698A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 151,902 control chromosomes in the GnomAD database, including 54,066 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54066 hom., cov: 30)
• Consequence: SEZ6L2 NM_001243332.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEZ6L2	NM_001243332.2	c.853+698A>G		intron_variant	Intron 5 of 17	ENST00000617533.5	NP_001230261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6L2	ENST00000617533.5	c.853+698A>G		intron_variant	Intron 5 of 17	1	NM_001243332.2	ENSP00000481917.1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 126856 AN: 151784 Hom.: 54013 Cov.: 30

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.944

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.875

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.834

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.836 AC: 126960 AN: 151902 Hom.: 54066 Cov.: 30 AF XY: 0.825 AC XY: 61216 AN XY: 74210

African (AFR) AF: 0.965 AC: 40027 AN: 41474

American (AMR) AF: 0.763 AC: 11596 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.875 AC: 3038 AN: 3472

East Asian (EAS) AF: 0.582 AC: 2990 AN: 5138

South Asian (SAS) AF: 0.473 AC: 2277 AN: 4814

European-Finnish (FIN) AF: 0.757 AC: 7969 AN: 10526

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56179 AN: 67964

Other (OTH) AF: 0.831 AC: 1753 AN: 2110

Alfa AF: 0.822 Hom.: 44923

Bravo AF: 0.849

Asia WGS AF: 0.558 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.46
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13332660; hg19: chr16-29905882;