chr2-100974981-A-C

Position:

• chr2-100974981-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.1282+37A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 1,607,718 control chromosomes in the GnomAD database, including 98,068 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 (13692 hom., cov: 32)
  • Exomes 𝑓: 0.32 (84376 hom.)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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-AS1 (HGNC:40408): (NPAS2 antisense RNA 1)

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 (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS2	NM_002518.4	c.1282+37A>C		intron_variant		ENST00000335681.10
NPAS2-AS1	NR_110213.1	n.575+304T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10	c.1282+37A>C		intron_variant		1	NM_002518.4	P1
NPAS2-AS1	ENST00000652285.1	n.605+304T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60753 AN: 151856 Hom.: 13653 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.344

GnomAD3 exomes AF: 0.397 AC: 97316 AN: 244860 Hom.: 22319 AF XY: 0.387 AC XY: 51158 AN XY: 132200

Gnomad AFR exome AF: 0.550

Gnomad AMR exome AF: 0.488

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.792

Gnomad SAS exome AF: 0.467

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.324 AC: 471323 AN: 1455744 Hom.: 84376 Cov.: 33 AF XY: 0.326 AC XY: 236036 AN XY: 724058

Gnomad4 AFR exome AF: 0.550

Gnomad4 AMR exome AF: 0.477

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.746

Gnomad4 SAS exome AF: 0.463

Gnomad4 FIN exome AF: 0.415

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.400 AC: 60856 AN: 151974 Hom.: 13692 Cov.: 32 AF XY: 0.409 AC XY: 30364 AN XY: 74268

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.352

Alfa AF: 0.299 Hom.: 14400

Bravo AF: 0.403

Asia WGS AF: 0.637 AC: 2213 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	2.1
DANN	Benign	0.39

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: rs2305159; hg19: chr2-101591443;