rs6725296

Variant names:

• chr2-100921242-G-A
• rs6725296
• NM_002518.4:c.33-3904G>A

Variant summary

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

The NM_002518.4(NPAS2):​c.33-3904G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,156 control chromosomes in the GnomAD database, including 5,029 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 0.24 (5029 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.33-3904G>A		intron_variant	Intron 2 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.33-3904G>A		intron_variant	Intron 2 of 20	1	NM_002518.4	ENSP00000338283.5
NPAS2	ENST00000427413.5	c.228-3904G>A		intron_variant	Intron 2 of 5	3		ENSP00000397595.2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35877 AN: 152038 Hom.: 5025 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.236 AC: 35899 AN: 152156 Hom.: 5029 Cov.: 32 AF XY: 0.234 AC XY: 17380 AN XY: 74368

African (AFR) AF: 0.382 AC: 15839 AN: 41476

American (AMR) AF: 0.186 AC: 2842 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3470

East Asian (EAS) AF: 0.151 AC: 780 AN: 5180

South Asian (SAS) AF: 0.249 AC: 1200 AN: 4822

European-Finnish (FIN) AF: 0.118 AC: 1251 AN: 10600

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12388 AN: 67994

Other (OTH) AF: 0.236 AC: 499 AN: 2112

Alfa AF: 0.204 Hom.: 606

Bravo AF: 0.246

Asia WGS AF: 0.203 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.42
PhyloP100		-0.36
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

Publications

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Other links and lift over

dbSNP: rs6725296; hg19: chr2-101537704;