NM_002518.4:c.599-1066G>T

Variant names:

• chr2-100962992-G-T
• rs12622050
• NM_002518.4:c.599-1066G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002518.4(NPAS2):​c.599-1066G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 15 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.599-1066G>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.599-1066G>T		intron_variant	Intron 7 of 20	1	NM_002518.4	ENSP00000338283.5
NPAS2	ENST00000448812.5	c.566-5289G>T		intron_variant	Intron 5 of 6	5		ENSP00000388528.1
NPAS2	ENST00000486017.5	n.645+159G>T		intron_variant	Intron 6 of 6	3
NPAS2	ENST00000492373.1	n.376-1066G>T		intron_variant	Intron 4 of 5	4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.81
PhyloP100		1.2

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: rs12622050; hg19: chr2-101579454;