2-100996153-T-C

Variant names:

• chr2-100996153-T-C
• rs1053096
• NM_002518.4:c.*571T>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.*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
• Publications: 13 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]

ENSG00000223947 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	NM_002518.4	MANE Select	c.*571T>C		3_prime_UTR	Exon 21 of 21	NP_002509.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPAS2	ENST00000335681.10	TSL:1 MANE Select	c.*571T>C		3_prime_UTR	Exon 21 of 21	ENSP00000338283.5
	ENSG00000223947	ENST00000452364.1	TSL:1	n.1152-144A>G		intron	N/A
	NPAS2	ENST00000906777.1		c.*571T>C		3_prime_UTR	Exon 22 of 22	ENSP00000576836.1

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

African (AFR) AF: 0.501 AC: 1677 AN: 3350

American (AMR) AF: 0.590 AC: 2867 AN: 4856

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 1654 AN: 2230

East Asian (EAS) AF: 0.379 AC: 1758 AN: 4638

South Asian (SAS) AF: 0.577 AC: 8670 AN: 15016

European-Finnish (FIN) AF: 0.586 AC: 2219 AN: 3786

Middle Eastern (MID) AF: 0.659 AC: 261 AN: 396

European-Non Finnish (NFE) AF: 0.681 AC: 57214 AN: 84012

Other (OTH) AF: 0.631 AC: 3433 AN: 5440

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

African (AFR) AF: 0.505 AC: 20920 AN: 41464

American (AMR) AF: 0.599 AC: 9154 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2571 AN: 3472

East Asian (EAS) AF: 0.392 AC: 2023 AN: 5164

South Asian (SAS) AF: 0.596 AC: 2870 AN: 4814

European-Finnish (FIN) AF: 0.595 AC: 6293 AN: 10574

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46557 AN: 67968

Other (OTH) AF: 0.634 AC: 1337 AN: 2110

Alfa AF: 0.669 Hom.: 58345

Bravo AF: 0.605

Asia WGS AF: 0.484 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.064
DANN	Benign	0.31
PhyloP100		-0.93
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: rs1053096; hg19: chr2-101612615;