chr15-96332277-G-C

Variant names:

• chr15-96332277-G-C
• rs775842693
• NM_021005.4:c.172G>C

Variant summary

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

The NM_021005.4(NR2F2):​c.172G>C​(p.Gly58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NR2F2 NM_021005.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.997
• Publications: 0 publications found

Genes affected

NR2F2 (HGNC:7976): (nuclear receptor subfamily 2 group F member 2) This gene encodes a member of the steroid thyroid hormone superfamily of nuclear receptors. The encoded protein is a ligand inducible transcription factor that is involved in the regulation of many different genes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

NR2F2-AS1 (HGNC:44222): (NR2F2 antisense RNA 1)

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=0.21973556).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021005.4. 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
	NR2F2	NM_021005.4	MANE Select	c.172G>C	p.Gly58Arg	missense	Exon 1 of 3	NP_066285.1	F1D8R0
	NR2F2	NM_001145155.2		c.44-1799G>C		intron	N/A	NP_001138627.1	P24468-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2F2	ENST00000394166.8	TSL:1 MANE Select	c.172G>C	p.Gly58Arg	missense	Exon 1 of 3	ENSP00000377721.3	P24468-1
	NR2F2	ENST00000421109.6	TSL:1	c.44-1799G>C		intron	N/A	ENSP00000401674.2	P24468-2
	NR2F2	ENST00000961130.1		c.172G>C	p.Gly58Arg	missense	Exon 2 of 4	ENSP00000631189.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	NR2F2-related congenital heart defects (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Benign	0.57
DEOGEN2	Benign	0.32	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.0
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.45	N
REVEL	Uncertain	0.32
Sift	Benign	0.10	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.22		Gain of solvent accessibility (P = 0.0584)
MVP		0.77
MPC		1.8
ClinPred		0.045	T
GERP RS		1.4
PromoterAI		0.0086	Neutral
Varity_R		0.034
gMVP		0.22
Mutation Taster		=89/11	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

dbSNP: rs775842693; hg19: chr15-96875506;