NM_021005.4:c.110C>T

Variant names:

• chr15-96332215-C-T
• rs1236680025
• NM_021005.4:c.110C>T

Variant summary

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

The NM_021005.4(NR2F2):​c.110C>T​(p.Pro37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000789 in 1,267,116 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P37R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: NR2F2 NM_021005.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.110C>T	p.Pro37Leu	missense	Exon 1 of 3	NP_066285.1	F1D8R0
	NR2F2	NM_001145155.2		c.44-1861C>T		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.110C>T	p.Pro37Leu	missense	Exon 1 of 3	ENSP00000377721.3	P24468-1
	NR2F2	ENST00000421109.6	TSL:1	c.44-1861C>T		intron	N/A	ENSP00000401674.2	P24468-2
	NR2F2	ENST00000961130.1		c.110C>T	p.Pro37Leu	missense	Exon 2 of 4	ENSP00000631189.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.89e-7 AC: 1 AN: 1267116 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 623546

African (AFR) AF: 0.00 AC: 0 AN: 25224

American (AMR) AF: 0.00 AC: 0 AN: 21296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20246

East Asian (EAS) AF: 0.00 AC: 0 AN: 27420

South Asian (SAS) AF: 0.00 AC: 0 AN: 61620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4192

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1017746

Other (OTH) AF: 0.0000194 AC: 1 AN: 51488

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.77	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Uncertain	0.76	D
MutationAssessor	Benign	1.8	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.85	N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.077	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.21		Loss of glycosylation at P37 (P = 0.0195)
MVP		0.76
MPC		1.5
ClinPred		0.93	D
GERP RS		4.6
PromoterAI		0.036	Neutral
Varity_R		0.34
gMVP		0.29
Mutation Taster		=16/84	disease causing

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: rs1236680025; hg19: chr15-96875444;