chr15-96326346-G-A

Position:

• chr15-96326346-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The ENST00000421109.6(NR2F2):​c.37G>A​(p.Gly13Ser) 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NR2F2 ENST00000421109.6 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.93

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

Verdict is Uncertain_significance. Variant got 2 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 4.1944 (greater than threshold 3.09). GenCC has associacion of gene with congenital heart defects, multiple types, 4, NR2F2 related multiple congenital anomalies/dysmorphic syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.30003798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F2-AS1	NR_125738.1	n.163+610C>T		intron_variant, non_coding_transcript_variant
NR2F2	NM_001145155.2	c.37G>A	p.Gly13Ser	missense_variant	1/3
NR2F2-AS1	NR_102743.1	n.163+853C>T		intron_variant, non_coding_transcript_variant
NR2F2-AS1	NR_102744.1	n.163+853C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F2-AS1	ENST00000560800.5	n.66+610C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

NR2F2-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 14, 2024

The NR2F2 c.37G>A variant is predicted to result in the amino acid substitution p.Gly13Ser. To our knowledge, this variant has not been reported in the literature or in gnomAD, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.28	D
MutationTaster	Benign	1.0	N
PROVEAN	Benign	0.94	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.055	T
Vest4		0.32
MutPred		0.52		Loss of helix (P = 0.0068);
MVP		0.79
ClinPred		0.90	D
GERP RS		5.2

Splicing

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: chr15-96869575;