Genetic Variant SEZ6L2:c.853+34G>A (chr16-29895225-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117

Publications

10 publications found

Variant links:

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]

SEZ6L2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243332.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEZ6L2	NM_001243332.2	MANE Select	c.853+34G>A	intron	N/A	NP_001230261.1	A0A087WYL5
SEZ6L2	NM_201575.4		c.853+34G>A	intron	N/A	NP_963869.2	Q6UXD5-1
SEZ6L2	NM_001243333.2		c.721+34G>A	intron	N/A	NP_001230262.1	Q6UXD5-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEZ6L2	ENST00000617533.5	TSL:1 MANE Select	c.853+34G>A	intron	N/A	ENSP00000481917.1	A0A087WYL5
SEZ6L2	ENST00000308713.9	TSL:1	c.853+34G>A	intron	N/A	ENSP00000312550.5	Q6UXD5-1
SEZ6L2	ENST00000350527.7	TSL:1	c.643+34G>A	intron	N/A	ENSP00000310206.3	Q6UXD5-3

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40778

AN:

150952

Hom.:

6138

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.295

AC:

73236

AN:

248588

AF XY:

0.296

show subpopulations

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 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.:

AF XY:

0.316

AC XY:

218201

AN XY:

690730

show subpopulations

African (AFR)

AF:

0.132

AC:

4246

AN:

32186

American (AMR)

AF:

0.220

AC:

9691

AN:

44064

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

6982

AN:

25512

East Asian (EAS)

AF:

0.342

AC:

13408

AN:

39218

South Asian (SAS)

AF:

0.218

AC:

18416

AN:

84658

European-Finnish (FIN)

AF:

0.336

AC:

17851

AN:

53102

Middle Eastern (MID)

AF:

0.201

AC:

1116

AN:

5542

European-Non Finnish (NFE)

AF:

0.336

AC:

348484

AN:

1038236

Other (OTH)

AF:

0.300

AC:

17327

AN:

57704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12797

25594

38392

51189

63986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10698

21396

32094

42792

53490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.270

AC:

40767

AN:

151072

Hom.:

6136

Cov.:

AF XY:

0.267

AC XY:

19661

AN XY:

73658

show subpopulations

African (AFR)

AF:

0.148

AC:

6116

AN:

41246

American (AMR)

AF:

0.217

AC:

3291

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

919

AN:

3462

East Asian (EAS)

AF:

0.400

AC:

2030

AN:

5074

South Asian (SAS)

AF:

0.198

AC:

951

AN:

4794

European-Finnish (FIN)

AF:

0.345

AC:

3538

AN:

10250

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.341

AC:

23135

AN:

67820

Other (OTH)

AF:

0.239

AC:

501

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1395

2790

4185

5580

6975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.287

Hom.:

1646

Bravo

AF:

0.257

Asia WGS

AF:

0.229

AC:

794

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.0

(source)

DANN

Benign

0.69

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over