2-218634144-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_032726.4(PLCD4):c.1646G>A(p.Arg549His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,582 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. R549C) has been classified as Uncertain significance.
Frequency
Consequence
NM_032726.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLCD4 | NM_032726.4 | c.1646G>A | p.Arg549His | missense_variant | 12/16 | ENST00000450993.7 | |
ZNF142 | NM_001379659.1 | c.*4195C>T | 3_prime_UTR_variant | 11/11 | ENST00000411696.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLCD4 | ENST00000450993.7 | c.1646G>A | p.Arg549His | missense_variant | 12/16 | 1 | NM_032726.4 | P1 | |
ZNF142 | ENST00000411696.7 | c.*4195C>T | 3_prime_UTR_variant | 11/11 | 5 | NM_001379659.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000487 AC: 12AN: 246480Hom.: 0 AF XY: 0.0000374 AC XY: 5AN XY: 133688
GnomAD4 exome AF: 0.0000370 AC: 54AN: 1460248Hom.: 0 Cov.: 32 AF XY: 0.0000427 AC XY: 31AN XY: 726274
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152334Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6AN XY: 74496
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 29, 2022 | The c.1646G>A (p.R549H) alteration is located in exon 12 (coding exon 11) of the PLCD4 gene. This alteration results from a G to A substitution at nucleotide position 1646, causing the arginine (R) at amino acid position 549 to be replaced by a histidine (H). 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