rs6738097

chr2-100962080-T-C

Variant summary

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

The NM_002518.4(NPAS2):c.599-1978T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,160 control chromosomes in the GnomAD database, including 2,435 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 0.17 (2435 hom., cov: 33)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPAS2	NM_002518.4	c.599-1978T>C		intron_variant		ENST00000335681.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPAS2	ENST00000335681.10	c.599-1978T>C		intron_variant		1	NM_002518.4	P1
NPAS2	ENST00000448812.5	c.567-6201T>C		intron_variant		5
NPAS2	ENST00000486017.5	n.567-675T>C		intron_variant, non_coding_transcript_variant		3
NPAS2	ENST00000492373.1	n.376-1978T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25670 AN: 152042 Hom.: 2433 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0733

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.169 AC: 25693 AN: 152160 Hom.: 2435 Cov.: 33 AF XY: 0.167 AC XY: 12420 AN XY: 74384

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.0881

Gnomad4 ASJ AF: 0.0733

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.144

Alfa AF: 0.137 Hom.: 1942

Bravo AF: 0.167

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	13
Dann	Benign	0.67

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: rs6738097; hg19: chr2-101578542;