Genetic Variant NPAS2:c.*524C>T (chr2-100996106-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002518.4(NPAS2):c.*524C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.282 in 496,326 control chromosomes in the GnomAD database, including 21,721 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5483 hom., cov: 32)

Exomes 𝑓: 0.30 ( 16238 hom. )

Consequence

NPAS2
NM_002518.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.68

Publications

21 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:

ENSG00000223947 (HGNC:):

ENSG00000223947 links:

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new If you want to explore the variant's impact on the transcript NM_002518.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002518.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	NM_002518.4	MANE Select	c.*524C>T		3_prime_UTR	Exon 21 of 21	NP_002509.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPAS2	ENST00000335681.10	TSL:1 MANE Select	c.*524C>T	3_prime_UTR	Exon 21 of 21	ENSP00000338283.5	Q99743
ENSG00000223947	ENST00000452364.1	TSL:1	n.1152-97G>A	intron	N/A
NPAS2	ENST00000906777.1		c.*524C>T	3_prime_UTR	Exon 22 of 22	ENSP00000576836.1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37716

AN:

151886

Hom.:

5486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0904

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.272

GnomAD4 exome

AF:

0.296

AC:

102005

AN:

344322

Hom.:

16238

Cov.:

AF XY:

0.300

AC XY:

51148

AN XY:

170598

show subpopulations

African (AFR)

AF:

0.0749

AC:

596

AN:

7962

American (AMR)

AF:

0.294

AC:

1880

AN:

6400

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

1821

AN:

4056

East Asian (EAS)

AF:

0.205

AC:

1305

AN:

6372

South Asian (SAS)

AF:

0.376

AC:

9285

AN:

24678

European-Finnish (FIN)

AF:

0.262

AC:

1378

AN:

5266

Middle Eastern (MID)

AF:

0.340

AC:

314

AN:

924

European-Non Finnish (NFE)

AF:

0.296

AC:

81533

AN:

275552

Other (OTH)

AF:

0.297

AC:

3893

AN:

13112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3427

6854

10281

13708

17135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2906

5812

8718

11624

14530

<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:

0.248

AC:

37713

AN:

152004

Hom.:

5483

Cov.:

AF XY:

0.249

AC XY:

18466

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0903

AC:

3744

AN:

41480

American (AMR)

AF:

0.285

AC:

4354

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

1574

AN:

3470

East Asian (EAS)

AF:

0.213

AC:

1100

AN:

5168

South Asian (SAS)

AF:

0.386

AC:

1859

AN:

4818

European-Finnish (FIN)

AF:

0.266

AC:

2806

AN:

10562

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21270

AN:

67922

Other (OTH)

AF:

0.271

AC:

571

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1383

2765

4148

5530

6913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.302

Hom.:

12388

Bravo

AF:

0.241

Asia WGS

AF:

0.289

AC:

1004

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

4.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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