chr2-100989274-A-T

Position:

• chr2-100989274-A-T

Variant summary

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

The NM_002518.4(NPAS2):​c.1828-982A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 153,446 control chromosomes in the GnomAD database, including 921 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 0.098 (906 hom., cov: 33)
  • Exomes 𝑓: 0.13 (15 hom.)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.1828-982A>T		intron_variant		ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.1828-982A>T		intron_variant		1	NM_002518.4	ENSP00000338283	P1

Frequencies

GnomAD3 genomes AF: 0.0978 AC: 14875 AN: 152104 Hom.: 906 Cov.: 33

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0951

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.128 AC: 157 AN: 1224 Hom.: 15 Cov.: 0 AF XY: 0.113 AC XY: 79 AN XY: 698

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0977 AC: 14879 AN: 152222 Hom.: 906 Cov.: 33 AF XY: 0.0982 AC XY: 7311 AN XY: 74414

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.0950

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0680

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.101

Alfa AF: 0.109 Hom.: 128

Bravo AF: 0.0915

Asia WGS AF: 0.0300 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.56

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: rs17662394; hg19: chr2-101605736;