NM_002518.4:c.598+3201C>T

Variant names:

• chr2-100952681-C-T
• rs11673746
• NM_002518.4:c.598+3201C>T

Variant summary

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

The NM_002518.4(NPAS2):​c.598+3201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,932 control chromosomes in the GnomAD database, including 8,709 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 0.33 (8709 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.598+3201C>T		intron_variant	Intron 7 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.598+3201C>T		intron_variant	Intron 7 of 20	1	NM_002518.4	ENSP00000338283.5
NPAS2	ENST00000448812.5	c.565+3201C>T		intron_variant	Intron 5 of 6	5		ENSP00000388528.1
NPAS2	ENST00000486017.5	n.566+3201C>T		intron_variant	Intron 5 of 6	3
NPAS2	ENST00000492373.1	n.375+3201C>T		intron_variant	Intron 4 of 5	4

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50824 AN: 151814 Hom.: 8713 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.0492

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.334 AC: 50818 AN: 151932 Hom.: 8709 Cov.: 32 AF XY: 0.331 AC XY: 24550 AN XY: 74252

African (AFR) AF: 0.344 AC: 14238 AN: 41420

American (AMR) AF: 0.310 AC: 4741 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1577 AN: 3468

East Asian (EAS) AF: 0.0491 AC: 254 AN: 5168

South Asian (SAS) AF: 0.227 AC: 1089 AN: 4804

European-Finnish (FIN) AF: 0.293 AC: 3079 AN: 10508

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24583 AN: 67972

Other (OTH) AF: 0.358 AC: 754 AN: 2104

Alfa AF: 0.355 Hom.: 3602

Bravo AF: 0.339

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.014
DANN	Benign	0.65
PhyloP100		-1.2
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: rs11673746; hg19: chr2-101569143;