rs12712085

Variant names:

• chr2-100948689-A-G
• rs12712085
• NM_002518.4:c.484+334A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002518.4(NPAS2):​c.484+334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,092 control chromosomes in the GnomAD database, including 32,388 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 0.65 (32388 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.484+334A>G		intron_variant	Intron 6 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.484+334A>G		intron_variant	Intron 6 of 20	1	NM_002518.4	ENSP00000338283.5
NPAS2	ENST00000448812.5	c.451+334A>G		intron_variant	Intron 4 of 6	5		ENSP00000388528.1
NPAS2	ENST00000486017.5	n.452+334A>G		intron_variant	Intron 4 of 6	3
NPAS2	ENST00000492373.1	n.261+334A>G		intron_variant	Intron 3 of 5	4

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98540 AN: 151974 Hom.: 32335 Cov.: 32

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.649 AC: 98651 AN: 152092 Hom.: 32388 Cov.: 32 AF XY: 0.655 AC XY: 48698 AN XY: 74364

African (AFR) AF: 0.754 AC: 31275 AN: 41480

American (AMR) AF: 0.686 AC: 10478 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2176 AN: 3472

East Asian (EAS) AF: 0.591 AC: 3065 AN: 5182

South Asian (SAS) AF: 0.685 AC: 3303 AN: 4820

European-Finnish (FIN) AF: 0.646 AC: 6822 AN: 10566

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39388 AN: 67980

Other (OTH) AF: 0.649 AC: 1369 AN: 2108

Alfa AF: 0.604 Hom.: 108104

Bravo AF: 0.653

Asia WGS AF: 0.648 AC: 2259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.44
PhyloP100		0.54
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: rs12712085; hg19: chr2-101565151;