Variant 2-100925274-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_002518.4(NPAS2):c.161G>C(p.Gly54Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000987 in 1,614,076 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 4 hom. )

Consequence

NPAS2
NM_002518.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.71

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, NPAS2

BP4

Computational evidence support a benign effect (MetaRNN=0.013000518).

BP6

Variant 2-100925274-G-C is Benign according to our data. Variant chr2-100925274-G-C is described in ClinVar as [Benign]. Clinvar id is 3040720.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 181 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS2	NM_002518.4 linkuse as main transcript	c.161G>C	p.Gly54Ala	missense_variant	3/21	ENST00000335681.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10 linkuse as main transcript	c.161G>C	p.Gly54Ala	missense_variant	3/21	1	NM_002518.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

181

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00148

AC:

371

AN:

251426

Hom.:

AF XY:

0.00140

AC XY:

190

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.00132

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.000966

AC:

1412

AN:

1461826

Hom.:

Cov.:

AF XY:

0.000961

AC XY:

699

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0113

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00318

Gnomad4 NFE exome

AF:

0.000783

Gnomad4 OTH exome

AF:

0.000993

GnomAD4 genome

AF:

0.00119

AC:

181

AN:

152250

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.000842

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00121

AC:

147

EpiCase

AF:

0.00136

EpiControl

AF:

0.000890

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

NPAS2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 16, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.020

Cadd

Pathogenic

Dann

Benign

0.94

DEOGEN2

Benign

0.42

T;.;.

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Uncertain

0.69

MutationAssessor

Benign

-0.46

N;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.94

N;.;N

REVEL

Uncertain

0.48

Sift

Benign

0.27

T;.;T

Sift4G

Benign

0.80

T;T;T

Polyphen

0.59

P;.;.

Vest4

0.50

MVP

0.61

MPC

1.8

ClinPred

0.028

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over