chr15-96332308-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_021005.4(NR2F2):c.203G>A(p.Ser68Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000442 in 1,583,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. S68G) has been classified as Likely benign.
Frequency
Consequence
NM_021005.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR2F2 | NM_021005.4 | c.203G>A | p.Ser68Asn | missense_variant | 1/3 | ENST00000394166.8 | |
NR2F2 | NM_001145155.2 | c.44-1768G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR2F2 | ENST00000394166.8 | c.203G>A | p.Ser68Asn | missense_variant | 1/3 | 1 | NM_021005.4 | P1 | |
NR2F2 | ENST00000421109.6 | c.44-1768G>A | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152056Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000501 AC: 1AN: 199424Hom.: 0 AF XY: 0.00000927 AC XY: 1AN XY: 107888
GnomAD4 exome AF: 0.00000419 AC: 6AN: 1431742Hom.: 0 Cov.: 31 AF XY: 0.00000423 AC XY: 3AN XY: 709678
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152056Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74270
ClinVar
Submissions by phenotype
Congenital heart defects, multiple types, 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NR2F2 protein function. This variant has not been reported in the literature in individuals affected with NR2F2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 68 of the NR2F2 protein (p.Ser68Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at