2-100895497-T-C

Position:

• chr2-100895497-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002518.4(NPAS2):​c.-22-9236T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,182 control chromosomes in the GnomAD database, including 45,794 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 0.77 (45794 hom., cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.-22-9236T>C		intron_variant		ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.-22-9236T>C		intron_variant		1	NM_002518.4	ENSP00000338283	P1
NPAS2	ENST00000427413.5	c.174-9236T>C		intron_variant		3		ENSP00000397595

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117201 AN: 152062 Hom.: 45742 Cov.: 33

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.771 AC: 117304 AN: 152182 Hom.: 45794 Cov.: 33 AF XY: 0.775 AC XY: 57647 AN XY: 74388

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.797

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.745

Alfa AF: 0.724 Hom.: 20125

Bravo AF: 0.760

Asia WGS AF: 0.781 AC: 2717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs1369481; hg19: chr2-101511959;