2-100844633-G-A

Position:

• chr2-100844633-G-A

Variant summary

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

The NM_002518.4(NPAS2):​c.-23+24219G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,002 control chromosomes in the GnomAD database, including 48,129 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 0.79 (48129 hom., cov: 31)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.-23+24219G>A		intron_variant		ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.-23+24219G>A		intron_variant		1	NM_002518.4	ENSP00000338283	P1
	ENST00000430586.1	n.333-2203G>A		intron_variant, non_coding_transcript_variant		3
NPAS2	ENST00000427413.5	c.173+23434G>A		intron_variant		3		ENSP00000397595

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119866 AN: 151884 Hom.: 48085 Cov.: 31

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.789 AC: 119962 AN: 152002 Hom.: 48129 Cov.: 31 AF XY: 0.792 AC XY: 58800 AN XY: 74288

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.782

Alfa AF: 0.717 Hom.: 25184

Bravo AF: 0.775

Asia WGS AF: 0.781 AC: 2719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.61

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: rs6722909; hg19: chr2-101461095;