chr2-100834217-A-G

Variant names:

• chr2-100834217-A-G
• rs3888170
• NM_002518.4:c.-23+13803A>G

Variant summary

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

The NM_002518.4(NPAS2):​c.-23+13803A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,968 control chromosomes in the GnomAD database, including 11,636 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 0.34 (11636 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 12 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]

ENSG00000289077 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 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.-23+13803A>G		intron	N/A	NP_002509.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	ENST00000335681.10	TSL:1 MANE Select	c.-23+13803A>G		intron	N/A	ENSP00000338283.5	Q99743
	NPAS2	ENST00000906777.1		c.-141+13803A>G		intron	N/A	ENSP00000576836.1
	NPAS2	ENST00000906778.1		c.-23+13633A>G		intron	N/A	ENSP00000576837.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51448 AN: 151850 Hom.: 11594 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.339 AC: 51546 AN: 151968 Hom.: 11636 Cov.: 32 AF XY: 0.339 AC XY: 25165 AN XY: 74314

African (AFR) AF: 0.624 AC: 25869 AN: 41426

American (AMR) AF: 0.288 AC: 4399 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3468

East Asian (EAS) AF: 0.589 AC: 3036 AN: 5154

South Asian (SAS) AF: 0.341 AC: 1640 AN: 4808

European-Finnish (FIN) AF: 0.206 AC: 2178 AN: 10594

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12759 AN: 67920

Other (OTH) AF: 0.307 AC: 648 AN: 2108

Alfa AF: 0.236 Hom.: 9098

Bravo AF: 0.360

Asia WGS AF: 0.528 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.3
DANN	Benign	0.63
PhyloP100		-0.027
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: rs3888170; hg19: chr2-101450679;