3-15003970-C-T

Variant names:

• chr3-15003970-C-T
• NM_001291694.2:c.56C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001291694.2(NR2C2):​c.56C>T​(p.Ser19Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S19S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NR2C2 NM_001291694.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15143955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291694.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2C2	NM_001291694.2	MANE Select	c.56C>T	p.Ser19Leu	missense	Exon 2 of 14	NP_001278623.1	P49116-1
	NR2C2	NM_003298.5		c.56C>T	p.Ser19Leu	missense	Exon 2 of 15	NP_003289.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2C2	ENST00000425241.6	TSL:2 MANE Select	c.56C>T	p.Ser19Leu	missense	Exon 2 of 14	ENSP00000388387.1	P49116-1
	NR2C2	ENST00000323373.10	TSL:1	c.56C>T	p.Ser19Leu	missense	Exon 2 of 15	ENSP00000320447.6	P49116-2
	NR2C2	ENST00000859246.1		c.56C>T	p.Ser19Leu	missense	Exon 3 of 16	ENSP00000529305.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	0.0034	D
MutationAssessor	Benign	0.81	L
PhyloP100		4.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.58	N
REVEL	Uncertain	0.30
Sift	Benign	0.29	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.64
MutPred		0.30		Gain of catalytic residue at S19 (P = 0.017)
MVP		0.32
MPC		0.32
ClinPred		0.45	T
GERP RS		5.3
PromoterAI		-0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.19
gMVP		0.12
Mutation Taster		=75/25	polymorphism

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

hg19: chr3-15045477;