NM_021005.4:c.103G>T

Variant names:

• chr15-96332208-G-T
• rs969342408
• NM_021005.4:c.103G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021005.4(NR2F2):​c.103G>T​(p.Gly35Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,520 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NR2F2 NM_021005.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.103G>T	p.Gly35Cys	missense_variant	Exon 1 of 3	ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.44-1868G>T		intron_variant	Intron 1 of 2		NP_001138627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.103G>T	p.Gly35Cys	missense_variant	Exon 1 of 3	1	NM_021005.4	ENSP00000377721.3
NR2F2	ENST00000421109.6	c.44-1868G>T		intron_variant	Intron 1 of 2	1		ENSP00000401674.2

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151520 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1205228 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 589134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151520 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74004

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.73	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Uncertain	0.61	D
MutationAssessor	Benign	1.4	L
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.54	N
REVEL	Uncertain	0.45
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.022	D
Polyphen		0.99	D
Vest4		0.43
MutPred		0.31		Gain of catalytic residue at P34 (P = 0.0545);
MVP		0.69
MPC		2.2
ClinPred		0.84	D
GERP RS		4.6
Varity_R		0.19
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs969342408; hg19: chr15-96875437;