dbSNP rs17662394: NPAS2:c.1828-982A>T (chr2-100989274-A-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_002518.4(NPAS2):c.1828-982A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 153,446 control chromosomes in the GnomAD database, including 921 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 0.098 ( 906 hom., cov: 33)

Exomes 𝑓: 0.13 ( 15 hom. )

Consequence

NPAS2
NM_002518.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19

Publications

0 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:

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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 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.1828-982A>T		intron	N/A	NP_002509.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPAS2	ENST00000335681.10	TSL:1 MANE Select	c.1828-982A>T	intron	N/A	ENSP00000338283.5	Q99743
NPAS2	ENST00000474550.5	TSL:1	n.6863-982A>T	intron	N/A
NPAS2	ENST00000906777.1		c.1828-982A>T	intron	N/A	ENSP00000576836.1

Frequencies

GnomAD3 genomes

AF:

0.0978

AC:

14875

AN:

152104

Hom.:

906

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0420

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.0951

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0682

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.128

AC:

157

AN:

1224

Hom.:

Cov.:

AF XY:

0.113

AC XY:

AN XY:

698

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AF:

0.122

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.153

AC:

AN:

European-Finnish (FIN)

AF:

0.208

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.128

AC:

113

AN:

880

Other (OTH)

AF:

0.100

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0977

AC:

14879

AN:

152222

Hom.:

906

Cov.:

AF XY:

0.0982

AC XY:

7311

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0420

AC:

1745

AN:

41544

American (AMR)

AF:

0.0950

AC:

1452

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0550

AC:

191

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5182

South Asian (SAS)

AF:

0.0680

AC:

328

AN:

4822

European-Finnish (FIN)

AF:

0.154

AC:

1628

AN:

10596

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9176

AN:

67994

Other (OTH)

AF:

0.101

AC:

214

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

677

1354

2030

2707

3384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.109

Hom.:

128

Bravo

AF:

0.0915

Asia WGS

AF:

0.0300

AC:

107

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.17

(source)

DANN

Benign

0.56

PhyloP100

-1.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over