2-100923328-G-A

Variant names:

• chr2-100923328-G-A
• rs356653
• NM_002518.4:c.33-1818G>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.33-1818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,960 control chromosomes in the GnomAD database, including 10,652 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 0.36 (10652 hom., cov: 31)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.93
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	NM_002518.4	MANE Select	c.33-1818G>A		intron	N/A	NP_002509.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	ENST00000335681.10	TSL:1 MANE Select	c.33-1818G>A		intron	N/A	ENSP00000338283.5
	NPAS2	ENST00000427413.5	TSL:3	c.228-1818G>A		intron	N/A	ENSP00000397595.2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54646 AN: 151844 Hom.: 10629 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.360 AC: 54710 AN: 151960 Hom.: 10652 Cov.: 31 AF XY: 0.367 AC XY: 27254 AN XY: 74290

African (AFR) AF: 0.437 AC: 18114 AN: 41416

American (AMR) AF: 0.511 AC: 7804 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1228 AN: 3468

East Asian (EAS) AF: 0.490 AC: 2521 AN: 5146

South Asian (SAS) AF: 0.452 AC: 2180 AN: 4818

European-Finnish (FIN) AF: 0.299 AC: 3166 AN: 10576

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18555 AN: 67954

Other (OTH) AF: 0.361 AC: 761 AN: 2108

Alfa AF: 0.310 Hom.: 4841

Bravo AF: 0.380

Asia WGS AF: 0.497 AC: 1729 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0020
DANN	Benign	0.59
PhyloP100		-4.9
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: rs356653; hg19: chr2-101539790;