chr2-100933719-G-A

Variant names:

• chr2-100933719-G-A
• rs13025524
• NM_002518.4:c.273+718G>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.273+718G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,126 control chromosomes in the GnomAD database, including 6,319 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 0.29 (6319 hom., cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 13 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 = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.273+718G>A		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+718G>A		intron_variant	Intron 4 of 20	1	NM_002518.4	ENSP00000338283.5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43562 AN: 152008 Hom.: 6317 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.286 AC: 43570 AN: 152126 Hom.: 6319 Cov.: 33 AF XY: 0.283 AC XY: 21052 AN XY: 74378

African (AFR) AF: 0.249 AC: 10323 AN: 41494

American (AMR) AF: 0.259 AC: 3963 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5166

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4822

European-Finnish (FIN) AF: 0.226 AC: 2390 AN: 10588

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

European-Non Finnish (NFE) AF: 0.325 AC: 22082 AN: 67986

Other (OTH) AF: 0.311 AC: 657 AN: 2112

Alfa AF: 0.317 Hom.: 12906

Bravo AF: 0.287

Asia WGS AF: 0.250 AC: 869 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	0.13
DANN	Benign	0.41
PhyloP100		-2.3
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: rs13025524; hg19: chr2-101550181;