rs1562313

chr2-100970993-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002518.4(NPAS2):c.1059C>T(p.Tyr353=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,612,266 control chromosomes in the GnomAD database, including 35,570 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 0.22 (3736 hom., cov: 32)
  • Exomes 𝑓: 0.21 (31834 hom.)
• Consequence: NPAS2 NM_002518.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS2	NM_002518.4	c.1059C>T	p.Tyr353=	synonymous_variant	12/21	ENST00000335681.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10	c.1059C>T	p.Tyr353=	synonymous_variant	12/21	1	NM_002518.4	P1
NPAS2	ENST00000474550.5	n.393C>T		non_coding_transcript_exon_variant	1/9	1
NPAS2-AS1	ENST00000652285.1	n.945G>A		non_coding_transcript_exon_variant	6/6
NPAS2	ENST00000448812.5	c.720C>T	p.Tyr240=	synonymous_variant	7/7	5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32972 AN: 151848 Hom.: 3731 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.189

GnomAD3 exomes AF: 0.193 AC: 48427 AN: 251312 Hom.: 5088 AF XY: 0.194 AC XY: 26331 AN XY: 135844

Gnomad AFR exome AF: 0.280

Gnomad AMR exome AF: 0.0814

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.248

Gnomad SAS exome AF: 0.209

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.206 AC: 300790 AN: 1460300 Hom.: 31834 Cov.: 31 AF XY: 0.206 AC XY: 149586 AN XY: 726506

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.0876

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.217 AC: 33000 AN: 151966 Hom.: 3736 Cov.: 32 AF XY: 0.215 AC XY: 16007 AN XY: 74288

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.188

Alfa AF: 0.199 Hom.: 7419

Bravo AF: 0.212

Asia WGS AF: 0.245 AC: 849 AN: 3478

EpiCase AF: 0.197

EpiControl AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.70
Dann	Benign	0.79
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

Other links and lift over

dbSNP: rs1562313; hg19: chr2-101587455; COSMIC: COSV59559304; COSMIC: COSV59559304;