2-11588803-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014668.4(GREB1):c.1217T>G(p.Leu406Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. L406V) has been classified as Uncertain significance.
Frequency
Consequence
NM_014668.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GREB1 | NM_014668.4 | c.1217T>G | p.Leu406Arg | missense_variant | 10/33 | ENST00000381486.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GREB1 | ENST00000381486.7 | c.1217T>G | p.Leu406Arg | missense_variant | 10/33 | 5 | NM_014668.4 | P1 | |
GREB1 | ENST00000234142.9 | c.1217T>G | p.Leu406Arg | missense_variant | 9/32 | 1 | P1 | ||
GREB1 | ENST00000432985.1 | c.119T>G | p.Leu40Arg | missense_variant | 1/9 | 1 | |||
GREB1 | ENST00000381483.6 | c.1217T>G | p.Leu406Arg | missense_variant | 10/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251488Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135920
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727230
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2022 | The c.1217T>G (p.L406R) alteration is located in exon 10 (coding exon 9) of the GREB1 gene. This alteration results from a T to G substitution at nucleotide position 1217, causing the leucine (L) at amino acid position 406 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