chr5-139848479-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004883.3(NRG2):c.1991C>G(p.Pro664Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,339,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. P664S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004883.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRG2 | NM_004883.3 | c.1991C>G | p.Pro664Arg | missense_variant | 10/10 | ENST00000361474.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRG2 | ENST00000361474.6 | c.1991C>G | p.Pro664Arg | missense_variant | 10/10 | 1 | NM_004883.3 | A2 | |
ENST00000504413.1 | n.143+47G>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000141 AC: 2AN: 141930Hom.: 0 Cov.: 29
GnomAD4 exome AF: 0.0000184 AC: 22AN: 1197346Hom.: 0 Cov.: 34 AF XY: 0.0000189 AC XY: 11AN XY: 581862
GnomAD4 genome ? AF: 0.0000141 AC: 2AN: 141930Hom.: 0 Cov.: 29 AF XY: 0.0000144 AC XY: 1AN XY: 69344
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 01, 2023 | The c.2015C>G (p.P672R) alteration is located in exon 11 (coding exon 11) of the NRG2 gene. This alteration results from a C to G substitution at nucleotide position 2015, causing the proline (P) at amino acid position 672 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at