NM_002518.4:c.274-2120T>C

Variant names:

• chr2-100935633-T-C
• rs895521
• NM_002518.4:c.274-2120T>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.274-2120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,130 control chromosomes in the GnomAD database, including 54,147 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 0.84 (54147 hom., cov: 31)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520
• Publications: 16 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002518.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	NM_002518.4	MANE Select	c.274-2120T>C		intron	N/A	NP_002509.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	ENST00000335681.10	TSL:1 MANE Select	c.274-2120T>C		intron	N/A	ENSP00000338283.5
	NPAS2	ENST00000906777.1		c.274-2120T>C		intron	N/A	ENSP00000576836.1
	NPAS2	ENST00000906778.1		c.274-2120T>C		intron	N/A	ENSP00000576837.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127789 AN: 152012 Hom.: 54089 Cov.: 31

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.841 AC: 127906 AN: 152130 Hom.: 54147 Cov.: 31 AF XY: 0.846 AC XY: 62871 AN XY: 74350

African (AFR) AF: 0.914 AC: 37942 AN: 41498

American (AMR) AF: 0.882 AC: 13490 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2938 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5171 AN: 5180

South Asian (SAS) AF: 0.890 AC: 4278 AN: 4808

European-Finnish (FIN) AF: 0.830 AC: 8794 AN: 10590

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52523 AN: 67966

Other (OTH) AF: 0.837 AC: 1769 AN: 2114

Alfa AF: 0.799 Hom.: 45673

Bravo AF: 0.848

Asia WGS AF: 0.944 AC: 3282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.6
DANN	Benign	0.67
PhyloP100		0.52
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: rs895521; hg19: chr2-101552095;