2-100970993-C-T

Variant names:

• chr2-100970993-C-T
• rs1562313
• NM_002518.4:c.1059C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BA1

The NM_002518.4(NPAS2):​c.1059C>T​(p.Tyr353Tyr) 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. 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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002518.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	NM_002518.4	MANE Select	c.1059C>T	p.Tyr353Tyr	synonymous	Exon 12 of 21	NP_002509.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	ENST00000335681.10	TSL:1 MANE Select	c.1059C>T	p.Tyr353Tyr	synonymous	Exon 12 of 21	ENSP00000338283.5	Q99743
	NPAS2	ENST00000474550.5	TSL:1	n.393C>T		non_coding_transcript_exon	Exon 1 of 9
	NPAS2	ENST00000906777.1		c.1059C>T	p.Tyr353Tyr	synonymous	Exon 13 of 22	ENSP00000576836.1

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

GnomAD2 exomes AF: 0.193 AC: 48427 AN: 251312 AF XY: 0.194

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 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

African (AFR) AF: 0.273 AC: 9132 AN: 33446

American (AMR) AF: 0.0876 AC: 3918 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2805 AN: 26124

East Asian (EAS) AF: 0.222 AC: 8806 AN: 39686

South Asian (SAS) AF: 0.206 AC: 17795 AN: 86230

European-Finnish (FIN) AF: 0.223 AC: 11896 AN: 53398

Middle Eastern (MID) AF: 0.149 AC: 861 AN: 5764

European-Non Finnish (NFE) AF: 0.210 AC: 233219 AN: 1110586

Other (OTH) AF: 0.205 AC: 12358 AN: 60344

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

African (AFR) AF: 0.276 AC: 11423 AN: 41424

American (AMR) AF: 0.128 AC: 1961 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3466

East Asian (EAS) AF: 0.243 AC: 1251 AN: 5142

South Asian (SAS) AF: 0.205 AC: 986 AN: 4814

European-Finnish (FIN) AF: 0.225 AC: 2374 AN: 10552

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13948 AN: 67972

Other (OTH) AF: 0.188 AC: 395 AN: 2106

Alfa AF: 0.203 Hom.: 14677

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.70
DANN	Benign	0.79
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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