2-100933299-G-C

Variant names:

• chr2-100933299-G-C
• rs3754674
• NM_002518.4:c.273+298G>C

Variant summary

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

The NM_002518.4(NPAS2):​c.273+298G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,040 control chromosomes in the GnomAD database, including 8,652 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 0.33 (8652 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.273+298G>C		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.273+298G>C		intron_variant	Intron 4 of 20	1	NM_002518.4	ENSP00000338283.5

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50476 AN: 151922 Hom.: 8651 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.332 AC: 50482 AN: 152040 Hom.: 8652 Cov.: 32 AF XY: 0.331 AC XY: 24611 AN XY: 74316

African (AFR) AF: 0.255 AC: 10575 AN: 41478

American (AMR) AF: 0.293 AC: 4470 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3466

East Asian (EAS) AF: 0.240 AC: 1240 AN: 5164

South Asian (SAS) AF: 0.308 AC: 1487 AN: 4824

European-Finnish (FIN) AF: 0.376 AC: 3975 AN: 10572

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26439 AN: 67948

Other (OTH) AF: 0.347 AC: 731 AN: 2108

Alfa AF: 0.343 Hom.: 1272

Bravo AF: 0.322

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.45
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3754674; hg19: chr2-101549761;