Genetic Variant NPAS2:c.1282+37A>C (chr2-100974981-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002518.4(NPAS2):c.1282+37A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,607,718 control chromosomes in the GnomAD database, including 98,068 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 0.40 ( 13692 hom., cov: 32)

Exomes 𝑓: 0.32 ( 84376 hom. )

Consequence

NPAS2
NM_002518.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.320

Publications

20 publications found

Variant links:

Genes affected

NPAS2 (HGNC:7895): (neuronal PAS domain protein 2) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors. A similar mouse protein may play a regulatory role in the acquisition of specific types of memory. It also may function as a part of a molecular clock operative in the mammalian forebrain. [provided by RefSeq, Jul 2008]

NPAS2 links:

NPAS2-AS1 (HGNC:40408): (NPAS2 antisense RNA 1)

NPAS2-AS1 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4 link	c.1282+37A>C		intron_variant	Intron 13 of 20	ENST00000335681.10	NP_002509.2	Q99743A2I2P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10 link	c.1282+37A>C		intron_variant	Intron 13 of 20	1	NM_002518.4	ENSP00000338283.5		Q99743

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60753

AN:

151856

Hom.:

13653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.482

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.344

GnomAD2 exomes

AF:

0.397

AC:

97316

AN:

244860

AF XY:

0.387

show subpopulations

Gnomad AFR exome

AF:

0.550

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.188

Gnomad EAS exome

AF:

0.792

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.327

GnomAD4 exome

AF:

0.324

AC:

471323

AN:

1455744

Hom.:

84376

Cov.:

AF XY:

0.326

AC XY:

236036

AN XY:

724058

show subpopulations

African (AFR)

AF:

0.550

AC:

18362

AN:

33356

American (AMR)

AF:

0.477

AC:

21109

AN:

44216

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

4840

AN:

25858

East Asian (EAS)

AF:

0.746

AC:

29530

AN:

39604

South Asian (SAS)

AF:

0.463

AC:

39603

AN:

85508

European-Finnish (FIN)

AF:

0.415

AC:

22007

AN:

53074

Middle Eastern (MID)

AF:

0.277

AC:

1590

AN:

5744

European-Non Finnish (NFE)

AF:

0.283

AC:

313192

AN:

1108232

Other (OTH)

AF:

0.351

AC:

21090

AN:

60152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

14509

29018

43527

58036

72545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10828

21656

32484

43312

54140

<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:

0.400

AC:

60856

AN:

151974

Hom.:

13692

Cov.:

AF XY:

0.409

AC XY:

30364

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.549

AC:

22736

AN:

41434

American (AMR)

AF:

0.409

AC:

6252

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

672

AN:

3468

East Asian (EAS)

AF:

0.774

AC:

3980

AN:

5142

South Asian (SAS)

AF:

0.482

AC:

2323

AN:

4824

European-Finnish (FIN)

AF:

0.424

AC:

4469

AN:

10542

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.284

AC:

19284

AN:

67982

Other (OTH)

AF:

0.352

AC:

741

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1728

3456

5185

6913

8641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.319

Hom.:

25050

Bravo

AF:

0.403

Asia WGS

AF:

0.637

AC:

2213

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.1

(source)

DANN

Benign

0.39

PhyloP100

-0.32

PromoterAI

-0.0069

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over