16-29872480-C-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001243332.2(SEZ6L2):c.2574G>C(p.Leu858=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,234 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (7 hom.)
• Consequence: SEZ6L2 NM_001243332.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.21

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-29872480-C-G is Benign according to our data. Variant chr16-29872480-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 727187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.21 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEZ6L2	NM_001243332.2	c.2574G>C	p.Leu858=	synonymous_variant	16/18	ENST00000617533.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEZ6L2	ENST00000617533.5	c.2574G>C	p.Leu858=	synonymous_variant	16/18	1	NM_001243332.2	P1

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 265 AN: 152238 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00159 AC: 400 AN: 251386 Hom.: 1 AF XY: 0.00157 AC XY: 214 AN XY: 135878

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00963

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000686

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.00219

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.00208 AC: 3044 AN: 1461878 Hom.: 7 Cov.: 32 AF XY: 0.00211 AC XY: 1536 AN XY: 727242

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00941

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000800

Gnomad4 FIN exome AF: 0.000524

Gnomad4 NFE exome AF: 0.00234

Gnomad4 OTH exome AF: 0.00142

GnomAD4 genome AF: 0.00174 AC: 265 AN: 152356 Hom.: 1 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74508

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00287

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00301 Hom.: 0

Bravo AF: 0.00160

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00289

EpiControl AF: 0.00202

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.21
Dann	Benign	0.61

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

Other links and lift over

dbSNP: rs145438044; hg19: chr16-29883801;