rs12622050

chr2-100962992-G-Achr2-100962992-G-Cchr2-100962992-G-T

Variant summary

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

The NM_002518.4(NPAS2):c.599-1066G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,162 control chromosomes in the GnomAD database, including 6,379 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 0.27 (6379 hom., cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS2	NM_002518.4	c.599-1066G>A		intron_variant		ENST00000335681.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10	c.599-1066G>A		intron_variant		1	NM_002518.4	P1
NPAS2	ENST00000448812.5	c.567-5289G>A		intron_variant		5
NPAS2	ENST00000486017.5	n.645+159G>A		intron_variant, non_coding_transcript_variant		3
NPAS2	ENST00000492373.1	n.376-1066G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41387 AN: 152044 Hom.: 6366 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.272 AC: 41444 AN: 152162 Hom.: 6379 Cov.: 33 AF XY: 0.281 AC XY: 20875 AN XY: 74378

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.251

Alfa AF: 0.223 Hom.: 8533

Bravo AF: 0.274

Asia WGS AF: 0.475 AC: 1650 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	0.19
Dann	Benign	0.79

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: rs12622050; hg19: chr2-101579454;