chr2-100974953-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002518.4(NPAS2):​c.1282+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,466 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 1 hom. )

Consequence

NPAS2
NM_002518.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.767
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-AS1 (HGNC:40408): (NPAS2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 2-100974953-G-A is Benign according to our data. Variant chr2-100974953-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 759157.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NPAS2NM_002518.4 linkuse as main transcriptc.1282+9G>A intron_variant ENST00000335681.10 NP_002509.2
NPAS2-AS1NR_110213.1 linkuse as main transcriptn.575+332C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NPAS2ENST00000335681.10 linkuse as main transcriptc.1282+9G>A intron_variant 1 NM_002518.4 ENSP00000338283 P1
NPAS2-AS1ENST00000652285.1 linkuse as main transcriptn.605+332C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152176
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000280
AC:
7
AN:
250286
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135202
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461290
Hom.:
1
Cov.:
35
AF XY:
0.0000179
AC XY:
13
AN XY:
726914
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152176
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.000314
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000663
Hom.:
0
Bravo
AF:
0.0000793

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.11
DANN
Benign
0.83

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

LitVar

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

Other links and lift over

dbSNP: rs369628388; hg19: chr2-101591415; API