NM_002518.4:c.364-2195C>G

Variant names:

• chr2-100946040-C-G
• rs10206435
• NM_002518.4:c.364-2195C>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.364-2195C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,104 control chromosomes in the GnomAD database, including 25,957 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 0.58 (25957 hom., cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.686
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 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.364-2195C>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.364-2195C>G		intron	N/A	ENSP00000338283.5
	NPAS2	ENST00000906777.1		c.364-2195C>G		intron	N/A	ENSP00000576836.1
	NPAS2	ENST00000906778.1		c.364-2195C>G		intron	N/A	ENSP00000576837.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88077 AN: 151986 Hom.: 25918 Cov.: 33

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.580 AC: 88169 AN: 152104 Hom.: 25957 Cov.: 33 AF XY: 0.584 AC XY: 43417 AN XY: 74360

African (AFR) AF: 0.674 AC: 27987 AN: 41514

American (AMR) AF: 0.650 AC: 9935 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2072 AN: 3464

East Asian (EAS) AF: 0.559 AC: 2883 AN: 5154

South Asian (SAS) AF: 0.578 AC: 2779 AN: 4812

European-Finnish (FIN) AF: 0.547 AC: 5785 AN: 10578

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34753 AN: 67988

Other (OTH) AF: 0.589 AC: 1243 AN: 2112

Alfa AF: 0.539 Hom.: 2731

Bravo AF: 0.591

Asia WGS AF: 0.569 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.3
DANN	Benign	0.41
PhyloP100		0.69
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: rs10206435; hg19: chr2-101562502;