2-100889540-T-C

Variant names:

• chr2-100889540-T-C
• rs17024926
• NM_002518.4:c.-22-15193T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002518.4(NPAS2):​c.-22-15193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,128 control chromosomes in the GnomAD database, including 9,042 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 0.34 (9042 hom., cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.-22-15193T>C		intron_variant	Intron 1 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.-22-15193T>C		intron_variant	Intron 1 of 20	1	NM_002518.4	ENSP00000338283.5
NPAS2	ENST00000427413.5	c.174-15193T>C		intron_variant	Intron 1 of 5	3		ENSP00000397595.2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51344 AN: 152010 Hom.: 9035 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.338 AC: 51366 AN: 152128 Hom.: 9042 Cov.: 33 AF XY: 0.343 AC XY: 25516 AN XY: 74354

African (AFR) AF: 0.310 AC: 12852 AN: 41502

American (AMR) AF: 0.306 AC: 4679 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2910 AN: 5162

South Asian (SAS) AF: 0.291 AC: 1404 AN: 4820

European-Finnish (FIN) AF: 0.497 AC: 5254 AN: 10566

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22546 AN: 67998

Other (OTH) AF: 0.300 AC: 635 AN: 2114

Alfa AF: 0.330 Hom.: 17429

Bravo AF: 0.323

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.76
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17024926; hg19: chr2-101506002; COSMIC: COSV59556487;