2-100996153-T-C

Position:

• chr2-100996153-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.*571T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 275,780 control chromosomes in the GnomAD database, including 55,205 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 0.61 (28875 hom., cov: 32)
  • Exomes 𝑓: 0.64 (26330 hom.)
• Consequence: NPAS2 NM_002518.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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]

ENSG00000223947 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.*571T>C		3_prime_UTR_variant	21/21	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.*571T>C		3_prime_UTR_variant	21/21	1	NM_002518.4	ENSP00000338283.5
ENSG00000223947	ENST00000452364.1	n.1152-144A>G		intron_variant		1
NPAS2	ENST00000495559.1	n.3165T>C		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92528 AN: 151938 Hom.: 28868 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.645 AC: 79753 AN: 123724 Hom.: 26330 Cov.: 4 AF XY: 0.641 AC XY: 41224 AN XY: 64346

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.742

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.577

Gnomad4 FIN exome AF: 0.586

Gnomad4 NFE exome AF: 0.681

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.609 AC: 92566 AN: 152056 Hom.: 28875 Cov.: 32 AF XY: 0.604 AC XY: 44907 AN XY: 74324

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.634

Alfa AF: 0.676 Hom.: 47343

Bravo AF: 0.605

Asia WGS AF: 0.484 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.064
DANN	Benign	0.31

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: rs1053096; hg19: chr2-101612615;