NM_002518.4:c.274-601C>T

Variant names:

• chr2-100937152-C-T
• rs17025005
• NM_002518.4:c.274-601C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002518.4(NPAS2):​c.274-601C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,130 control chromosomes in the GnomAD database, including 2,145 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 0.16 (2145 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 11 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.274-601C>T		intron_variant	Intron 4 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.274-601C>T		intron_variant	Intron 4 of 20	1	NM_002518.4	ENSP00000338283.5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24686 AN: 152012 Hom.: 2149 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.185

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24694 AN: 152130 Hom.: 2145 Cov.: 32 AF XY: 0.160 AC XY: 11930 AN XY: 74368

African (AFR) AF: 0.119 AC: 4944 AN: 41482

American (AMR) AF: 0.163 AC: 2489 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 824 AN: 3472

East Asian (EAS) AF: 0.236 AC: 1222 AN: 5170

South Asian (SAS) AF: 0.148 AC: 711 AN: 4818

European-Finnish (FIN) AF: 0.112 AC: 1188 AN: 10580

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12696 AN: 68002

Other (OTH) AF: 0.182 AC: 384 AN: 2112

Alfa AF: 0.184 Hom.: 3551

Bravo AF: 0.163

Asia WGS AF: 0.181 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.71
PhyloP100		-0.040
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: rs17025005; hg19: chr2-101553614; COSMIC: COSV59556589;