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GeneBe

2-100974910-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002518.4(NPAS2):c.1248C>T(p.His416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000766 in 1,614,032 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00049 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00079 ( 7 hom. )

Consequence

NPAS2
NM_002518.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.688
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 -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-100974910-C-T is Benign according to our data. Variant chr2-100974910-C-T is described in ClinVar as [Benign]. Clinvar id is 733860.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.688 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 73 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPAS2NM_002518.4 linkuse as main transcriptc.1248C>T p.His416= synonymous_variant 13/21 ENST00000335681.10
NPAS2-AS1NR_110213.1 linkuse as main transcriptn.575+375G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPAS2ENST00000335681.10 linkuse as main transcriptc.1248C>T p.His416= synonymous_variant 13/211 NM_002518.4 P1
NPAS2-AS1ENST00000652285.1 linkuse as main transcriptn.605+375G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000480
AC:
73
AN:
152176
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00642
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000485
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00115
AC:
289
AN:
251340
Hom.:
3
AF XY:
0.00154
AC XY:
209
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00568
Gnomad FIN exome
AF:
0.000416
Gnomad NFE exome
AF:
0.000827
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000795
AC:
1162
AN:
1461738
Hom.:
7
Cov.:
36
AF XY:
0.000986
AC XY:
717
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00570
Gnomad4 FIN exome
AF:
0.000468
Gnomad4 NFE exome
AF:
0.000495
Gnomad4 OTH exome
AF:
0.000961
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000486
AC:
74
AN:
152294
Hom.:
2
Cov.:
33
AF XY:
0.000604
AC XY:
45
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00663
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000485
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000622
Hom.:
1
Bravo
AF:
0.000359
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00115
EpiControl
AF:
0.00101

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.35
Cadd
Benign
9.2
Dann
Benign
0.89
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs200967952; hg19: chr2-101591372; API