chr14-90288542-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_017970.4(NRDE2):c.2833G>C(p.Glu945Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. E945K) has been classified as Uncertain significance.
Frequency
Consequence
NM_017970.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRDE2 | NM_017970.4 | c.2833G>C | p.Glu945Gln | missense_variant | 11/14 | ENST00000354366.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRDE2 | ENST00000354366.8 | c.2833G>C | p.Glu945Gln | missense_variant | 11/14 | 1 | NM_017970.4 | P1 | |
NRDE2 | ENST00000553409.5 | c.*2358G>C | 3_prime_UTR_variant, NMD_transcript_variant | 9/12 | 1 | ||||
NRDE2 | ENST00000556189.5 | c.*1311G>C | 3_prime_UTR_variant, NMD_transcript_variant | 7/10 | 1 | ||||
NRDE2 | ENST00000555903.1 | n.344G>C | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251400Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135884
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461804Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727198
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74370
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 18, 2023 | The c.2833G>C (p.E945Q) alteration is located in exon 11 (coding exon 11) of the NRDE2 gene. This alteration results from a G to C substitution at nucleotide position 2833, causing the glutamic acid (E) at amino acid position 945 to be replaced by a glutamine (Q). 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