2-100892437-A-G

Variant names:

• chr2-100892437-A-G
• rs12712083
• NM_002518.4:c.-22-12296A>G

Variant summary

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

The NM_002518.4(NPAS2):​c.-22-12296A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,916 control chromosomes in the GnomAD database, including 26,355 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 0.57 (26355 hom., cov: 31)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.-22-12296A>G		intron_variant	Intron 1 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.-22-12296A>G		intron_variant	Intron 1 of 20	1	NM_002518.4	ENSP00000338283.5
NPAS2	ENST00000427413.5	c.174-12296A>G		intron_variant	Intron 1 of 5	3		ENSP00000397595.2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85840 AN: 151798 Hom.: 26307 Cov.: 31

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.574

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.566 AC: 85943 AN: 151916 Hom.: 26355 Cov.: 31 AF XY: 0.570 AC XY: 42330 AN XY: 74264

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.573

Alfa AF: 0.460 Hom.: 20916

Bravo AF: 0.580

Asia WGS AF: 0.687 AC: 2390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.67
DANN	Benign	0.35

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: rs12712083; hg19: chr2-101508899;