Variant rs58728948 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002518.4(NPAS2):c.2068G>A(p.Ala690Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,614,170 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 22 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 18 hom. )

Consequence

NPAS2
NM_002518.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.68

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 (HGNC:):

NPAS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067507327).

BP6

Variant 2-100990829-G-A is Benign according to our data. Variant chr2-100990829-G-A is described in ClinVar as [Benign]. Clinvar id is 791865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00905 (1379/152316) while in subpopulation AFR AF= 0.031 (1288/41572). AF 95% confidence interval is 0.0296. There are 22 homozygotes in gnomad4. There are 664 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1379 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS2	NM_002518.4 linkuse as main transcript	c.2068G>A	p.Ala690Thr	missense_variant	19/21	ENST00000335681.10	NP_002509.2	Q99743A2I2P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10 linkuse as main transcript	c.2068G>A	p.Ala690Thr	missense_variant	19/21	1	NM_002518.4	ENSP00000338283.5		Q99743

Frequencies

GnomAD3 genomes

AF:

0.00907

AC:

1380

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0311

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00254

AC:

637

AN:

251234

Hom.:

AF XY:

0.00203

AC XY:

276

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.0314

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000370

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00104

AC:

1519

AN:

1461854

Hom.:

Cov.:

AF XY:

0.000891

AC XY:

648

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0303

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.00905

AC:

1379

AN:

152316

Hom.:

Cov.:

AF XY:

0.00892

AC XY:

664

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0310

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.0108

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0306

AC:

135

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00323

AC:

392

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0068

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.55

REVEL

Benign

0.077

Sift

Benign

0.045

Sift4G

Benign

0.18

Polyphen

0.29

Vest4

0.36

MVP

0.26

MPC

0.28

ClinPred

0.0037

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

gMVP

0.27

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

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