chr2-100941104-G-A

Variant names:

• chr2-100941104-G-A
• rs11674199
• NM_002518.4:c.363+3262G>A

Variant summary

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

The NM_002518.4(NPAS2):​c.363+3262G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,086 control chromosomes in the GnomAD database, including 8,333 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 (8333 hom., cov: 32)
• Consequence: NPAS2 NM_002518.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPAS2	NM_002518.4	c.363+3262G>A		intron_variant	Intron 5 of 20	ENST00000335681.10	NP_002509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPAS2	ENST00000335681.10	c.363+3262G>A		intron_variant	Intron 5 of 20	1	NM_002518.4	ENSP00000338283.5

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49524 AN: 151968 Hom.: 8337 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.0468

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.326 AC: 49520 AN: 152086 Hom.: 8333 Cov.: 32 AF XY: 0.322 AC XY: 23931 AN XY: 74372

African (AFR) AF: 0.314 AC: 13013 AN: 41488

American (AMR) AF: 0.309 AC: 4729 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1604 AN: 3470

East Asian (EAS) AF: 0.0467 AC: 242 AN: 5182

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4818

European-Finnish (FIN) AF: 0.289 AC: 3055 AN: 10584

Middle Eastern (MID) AF: 0.490 AC: 142 AN: 290

European-Non Finnish (NFE) AF: 0.361 AC: 24543 AN: 67952

Other (OTH) AF: 0.357 AC: 754 AN: 2110

Alfa AF: 0.357 Hom.: 42013

Bravo AF: 0.330

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.88
PhyloP100		-0.69
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: rs11674199; hg19: chr2-101557566; COSMIC: COSV59562652; COSMIC: COSV59562652;