chr15-96332114-G-A

Position:

• chr15-96332114-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_021005.4(NR2F2):​c.9G>A​(p.Met3Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (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: 7.22

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), NR2F2. . Gene score misZ 3.5964 (greater than the threshold 3.09). Trascript score misZ 4.1992 (greater than threshold 3.09). GenCC has associacion of gene with congenital heart defects, multiple types, 4, NR2F2 related multiple congenital anomalies/dysmorphic syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F2	NM_021005.4	c.9G>A	p.Met3Ile	missense_variant	1/3	ENST00000394166.8	NP_066285.1
NR2F2	NM_001145155.2	c.44-1962G>A		intron_variant			NP_001138627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR2F2	ENST00000394166.8	c.9G>A	p.Met3Ile	missense_variant	1/3	1	NM_021005.4	ENSP00000377721	P1
NR2F2	ENST00000421109.6	c.44-1962G>A		intron_variant		1		ENSP00000401674

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1189236 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 578566

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 Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T
Eigen	Benign	-0.0010
Eigen_PC	Benign	0.13
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.47
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.066	T
Polyphen		0.0010	B
Vest4		0.59
MutPred		0.43		Gain of catalytic residue at M3 (P = 0.0524);
MVP		0.95
MPC		1.6
ClinPred		0.93	D
GERP RS		3.6
Varity_R		0.52
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-96875343;