16-29895225-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243332.2(SEZ6L2):c.853+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,531,294 control chromosomes in the GnomAD database, including 78,688 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 0.27 (6136 hom., cov: 29)
  • Exomes 𝑓: 0.32 (72552 hom.)
• Consequence: SEZ6L2 NM_001243332.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L2	NM_001243332.2	c.853+34G>A		intron_variant		ENST00000617533.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L2	ENST00000617533.5	c.853+34G>A		intron_variant		1	NM_001243332.2	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40778 AN: 150952 Hom.: 6138 Cov.: 29

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.242

GnomAD3 exomes AF: 0.295 AC: 73236 AN: 248588 Hom.: 11579 AF XY: 0.296 AC XY: 39788 AN XY: 134466

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.415

Gnomad SAS exome AF: 0.213

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.277

GnomAD4 exome AF: 0.317 AC: 437521 AN: 1380222 Hom.: 72552 Cov.: 23 AF XY: 0.316 AC XY: 218201 AN XY: 690730

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.218

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.270 AC: 40767 AN: 151072 Hom.: 6136 Cov.: 29 AF XY: 0.267 AC XY: 19661 AN XY: 73658

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.239

Alfa AF: 0.290 Hom.: 1634

Bravo AF: 0.257

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.0
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs4787484; hg19: chr16-29906546; COSMIC: COSV58099707; COSMIC: COSV58099707;