chr2-100934525-A-C

Position:

• chr2-100934525-A-C

Variant summary

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

The NM_002518.4(NPAS2):​c.273+1524A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,120 control chromosomes in the GnomAD database, including 4,093 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 0.22 (4093 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS2	NM_002518.4	c.273+1524A>C		intron_variant		ENST00000335681.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10	c.273+1524A>C		intron_variant		1	NM_002518.4	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33784 AN: 152002 Hom.: 4097 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.222 AC: 33789 AN: 152120 Hom.: 4093 Cov.: 32 AF XY: 0.222 AC XY: 16506 AN XY: 74360

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.237

Alfa AF: 0.244 Hom.: 6437

Bravo AF: 0.216

Asia WGS AF: 0.266 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.53

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: rs3768984; hg19: chr2-101550987;