2-100978773-A-G

Position:

• chr2-100978773-A-G

Variant summary

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

The ENST00000335681.10(NPAS2):​c.1482+974A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,074 control chromosomes in the GnomAD database, including 13,499 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 0.40 (13499 hom., cov: 33)
• Consequence: NPAS2 ENST00000335681.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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]

NPAS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.1482+974A>G		intron_variant		ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.1482+974A>G		intron_variant		1	NM_002518.4	ENSP00000338283.5
NPAS2	ENST00000474550.5	n.816+974A>G		intron_variant		1
NPAS2	ENST00000450763.1	c.279+974A>G		intron_variant		4		ENSP00000392125.1
NPAS2	ENST00000471974.1	n.342+974A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60494 AN: 151956 Hom.: 13470 Cov.: 33

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.398 AC: 60585 AN: 152074 Hom.: 13499 Cov.: 33 AF XY: 0.407 AC XY: 30287 AN XY: 74364

Gnomad4 AFR AF: 0.541

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.757

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.353

Alfa AF: 0.331 Hom.: 4769

Bravo AF: 0.400

Asia WGS AF: 0.628 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.63

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: rs1542179; hg19: chr2-101595235; COSMIC: COSV59559714; COSMIC: COSV59559714;