2-100905315-G-A

Variant names:

• chr2-100905315-G-A
• rs2117714
• NM_002518.4:c.32+529G>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.32+529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,630 control chromosomes in the GnomAD database, including 31,054 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 0.63 (31054 hom., cov: 30)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.32+529G>A		intron_variant	Intron 2 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.32+529G>A		intron_variant	Intron 2 of 20	1	NM_002518.4	ENSP00000338283.5
NPAS2	ENST00000427413.5	c.227+529G>A		intron_variant	Intron 2 of 5	3		ENSP00000397595.2

Frequencies

GnomAD3 genomes AF: 0.632 AC: 95705 AN: 151512 Hom.: 31025 Cov.: 30

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.632 AC: 95770 AN: 151630 Hom.: 31054 Cov.: 30 AF XY: 0.625 AC XY: 46264 AN XY: 74058

African (AFR) AF: 0.550 AC: 22718 AN: 41278

American (AMR) AF: 0.477 AC: 7254 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2209 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2855 AN: 5148

South Asian (SAS) AF: 0.534 AC: 2555 AN: 4784

European-Finnish (FIN) AF: 0.689 AC: 7239 AN: 10512

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48806 AN: 67930

Other (OTH) AF: 0.629 AC: 1321 AN: 2100

Alfa AF: 0.680 Hom.: 59727

Bravo AF: 0.613

Asia WGS AF: 0.512 AC: 1779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.79
PhyloP100		0.18
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: rs2117714; hg19: chr2-101521777; COSMIC: COSV59556521;