16-29876480-G-A

Variant names:

• chr16-29876480-G-A
• rs9926856
• NM_001243332.2:c.2104+276C>T

Variant summary

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

The NM_001243332.2(SEZ6L2):​c.2104+276C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,006 control chromosomes in the GnomAD database, including 2,264 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 0.10 (2264 hom., cov: 31)
• Consequence: SEZ6L2 NM_001243332.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.39
• Publications: 3 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 = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEZ6L2	NM_001243332.2	c.2104+276C>T		intron_variant	Intron 12 of 17	ENST00000617533.5	NP_001230261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEZ6L2	ENST00000617533.5	c.2104+276C>T		intron_variant	Intron 12 of 17	1	NM_001243332.2	ENSP00000481917.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15489 AN: 151888 Hom.: 2251 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00933

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.102 AC: 15543 AN: 152006 Hom.: 2264 Cov.: 31 AF XY: 0.101 AC XY: 7500 AN XY: 74338

African (AFR) AF: 0.306 AC: 12667 AN: 41364

American (AMR) AF: 0.0567 AC: 866 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1441 AN: 5150

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4818

European-Finnish (FIN) AF: 0.00933 AC: 99 AN: 10610

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.00231 AC: 157 AN: 68010

Other (OTH) AF: 0.0685 AC: 145 AN: 2116

Alfa AF: 0.0454 Hom.: 332

Bravo AF: 0.118

Asia WGS AF: 0.124 AC: 431 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	0.037
DANN	Benign	0.73
PhyloP100		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs9926856; hg19: chr16-29887801;