rs2117714

Positions:

• chr2-100905315-G-A
• chr2-100905315-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NPAS2	NM_002518.4	c.32+529G>A		intron_variant		ENST00000335681.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10	c.32+529G>A		intron_variant		1	NM_002518.4	P1
NPAS2	ENST00000427413.5	c.227+529G>A		intron_variant		3

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

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.637

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.629

Alfa AF: 0.687 Hom.: 47842

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2117714; hg19: chr2-101521777; COSMIC: COSV59556521;