NM_001291694.2:c.-40+18321A>G

Variant names:

• chr3-14966227-A-G
• rs1344825
• NM_001291694.2:c.-40+18321A>G

Variant summary

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

The NM_001291694.2(NR2C2):​c.-40+18321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,068 control chromosomes in the GnomAD database, including 14,766 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 0.39 (14766 hom., cov: 32)
• Consequence: NR2C2 NM_001291694.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.92
• Publications: 6 publications found

Genes affected

NR2C2 (HGNC:7972): (nuclear receptor subfamily 2 group C member 2) This gene encodes a protein that belongs to the nuclear hormone receptor family. Members of this family act as ligand-activated transcription factors and function in many biological processes such as development, cellular differentiation and homeostasis. The activated receptor/ligand complex is translocated to the nucleus where it binds to hormone response elements of target genes. The protein encoded by this gene plays a role in protecting cells from oxidative stress and damage induced by ionizing radiation. The lack of a similar gene in mouse results in growth retardation, severe spinal curvature, subfertility, premature aging, and prostatic intraepithelial neoplasia (PIN) development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2C2	NM_001291694.2	c.-40+18321A>G		intron_variant	Intron 1 of 13	ENST00000425241.6	NP_001278623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2C2	ENST00000425241.6	c.-40+18321A>G		intron_variant	Intron 1 of 13	2	NM_001291694.2	ENSP00000388387.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59688 AN: 151950 Hom.: 14721 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.393 AC: 59785 AN: 152068 Hom.: 14766 Cov.: 32 AF XY: 0.383 AC XY: 28493 AN XY: 74342

African (AFR) AF: 0.701 AC: 29063 AN: 41476

American (AMR) AF: 0.328 AC: 5022 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1130 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1376 AN: 5172

South Asian (SAS) AF: 0.244 AC: 1178 AN: 4822

European-Finnish (FIN) AF: 0.159 AC: 1685 AN: 10576

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19060 AN: 67954

Other (OTH) AF: 0.392 AC: 827 AN: 2108

Alfa AF: 0.304 Hom.: 4113

Bravo AF: 0.421

Asia WGS AF: 0.287 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.033
DANN	Benign	0.30
PhyloP100		-3.9
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: rs1344825; hg19: chr3-15007734;