2-119158224-C-T

Variant summary

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

The NM_182528.4(C1QL2):​c.46G>A​(p.Ala16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

C1QL2
NM_182528.4 missense

Scores

2
1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08
Variant links:
Genes affected
C1QL2 (HGNC:24181): (complement C1q like 2) Predicted to enable identical protein binding activity. Predicted to be located in extracellular region. Predicted to be part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.33577156).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C1QL2NM_182528.4 linkc.46G>A p.Ala16Thr missense_variant Exon 1 of 2 ENST00000272520.4 NP_872334.2 Q7Z5L3A0A3B0IND4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C1QL2ENST00000272520.4 linkc.46G>A p.Ala16Thr missense_variant Exon 1 of 2 1 NM_182528.4 ENSP00000272520.3 Q7Z5L3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1419966
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
705936
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.46G>A (p.A16T) alteration is located in exon 1 (coding exon 1) of the C1QL2 gene. This alteration results from a G to A substitution at nucleotide position 46, causing the alanine (A) at amino acid position 16 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.074
FATHMM_MKL
Benign
0.59
D
LIST_S2
Benign
0.59
T
M_CAP
Pathogenic
0.98
D
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
0.41
N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.73
N
REVEL
Benign
0.19
Sift
Benign
0.13
T
Sift4G
Benign
0.18
T
Polyphen
0.59
P
Vest4
0.069
MutPred
0.30
Loss of helix (P = 0.0376);
MVP
0.81
MPC
0.94
ClinPred
0.54
D
GERP RS
4.0
Varity_R
0.15
gMVP
0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-119915800; API