chr2-100896081-G-A

Variant names:

• chr2-100896081-G-A
• rs17654772
• NM_002518.4:c.-22-8652G>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.-22-8652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,150 control chromosomes in the GnomAD database, including 3,858 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 0.19 (3858 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 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.-22-8652G>A		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.-22-8652G>A		intron	N/A	ENSP00000338283.5	Q99743
	NPAS2	ENST00000906777.1		c.-140-3168G>A		intron	N/A	ENSP00000576836.1
	NPAS2	ENST00000906778.1		c.-22-8652G>A		intron	N/A	ENSP00000576837.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29313 AN: 152032 Hom.: 3856 Cov.: 32

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.193 AC: 29311 AN: 152150 Hom.: 3858 Cov.: 32 AF XY: 0.193 AC XY: 14382 AN XY: 74374

African (AFR) AF: 0.0492 AC: 2044 AN: 41544

American (AMR) AF: 0.143 AC: 2182 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3470

East Asian (EAS) AF: 0.0604 AC: 312 AN: 5166

South Asian (SAS) AF: 0.121 AC: 582 AN: 4820

European-Finnish (FIN) AF: 0.396 AC: 4187 AN: 10580

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19062 AN: 67960

Other (OTH) AF: 0.165 AC: 348 AN: 2108

Alfa AF: 0.241 Hom.: 12301

Bravo AF: 0.166

Asia WGS AF: 0.0890 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.25
PhyloP100		-0.84
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: rs17654772; hg19: chr2-101512543; COSMIC: COSV59554880;