chr19-58551759-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014453.4(CHMP2A):​c.559G>A​(p.Gly187Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G187R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHMP2A
NM_014453.4 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.39
Variant links:
Genes affected
CHMP2A (HGNC:30216): (charged multivesicular body protein 2A) CHMP2A belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).[supplied by OMIM, Mar 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27958524).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHMP2ANM_014453.4 linkc.559G>A p.Gly187Ser missense_variant Exon 6 of 6 ENST00000312547.7 NP_055268.1 O43633A0A024R4S0
CHMP2ANM_198426.3 linkc.559G>A p.Gly187Ser missense_variant Exon 6 of 6 NP_940818.1 O43633A0A024R4S0
CHMP2AXM_005258746.3 linkc.688G>A p.Gly230Ser missense_variant Exon 5 of 5 XP_005258803.1 M0R1T5
CHMP2AXM_005258747.4 linkc.688G>A p.Gly230Ser missense_variant Exon 5 of 5 XP_005258804.1 M0R1T5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHMP2AENST00000312547.7 linkc.559G>A p.Gly187Ser missense_variant Exon 6 of 6 1 NM_014453.4 ENSP00000310440.1 O43633

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461856
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Uncertain
0.055
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
22
DANN
Benign
0.89
DEOGEN2
Benign
0.057
T;T;T
Eigen
Benign
-0.19
Eigen_PC
Benign
0.022
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
.;.;D
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.28
T;T;T
MetaSVM
Benign
-0.80
T
MutationAssessor
Benign
1.4
L;L;L
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.9
.;.;N
REVEL
Uncertain
0.34
Sift
Benign
0.34
.;.;T
Sift4G
Benign
0.75
T;T;T
Polyphen
0.044
B;B;B
Vest4
0.40
MutPred
0.44
Gain of phosphorylation at G187 (P = 0.023);Gain of phosphorylation at G187 (P = 0.023);Gain of phosphorylation at G187 (P = 0.023);
MVP
0.71
MPC
0.59
ClinPred
0.87
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149478183; hg19: chr19-59063126; API