2-119157926-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_182528.4(C1QL2):​c.344G>A​(p.Gly115Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000064 in 1,546,528 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 (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

C1QL2
NM_182528.4 missense

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.982

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C1QL2NM_182528.4 linkc.344G>A p.Gly115Glu 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.344G>A p.Gly115Glu missense_variant Exon 1 of 2 1 NM_182528.4 ENSP00000272520.3 Q7Z5L3

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152140
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000347
AC:
5
AN:
144200
Hom.:
0
AF XY:
0.0000256
AC XY:
2
AN XY:
78260
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000952
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000624
AC:
87
AN:
1394388
Hom.:
0
Cov.:
37
AF XY:
0.0000553
AC XY:
38
AN XY:
687750
show subpopulations
Gnomad4 AFR exome
AF:
0.0000317
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000278
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000789
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152140
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000157
Hom.:
0
Bravo
AF:
0.0000869
ExAC
AF:
0.0000344
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 16, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.344G>A (p.G115E) 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 344, causing the glycine (G) at amino acid position 115 to be replaced by a glutamic acid (E). 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
Pathogenic
0.67
BayesDel_addAF
Uncertain
0.070
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.80
D
Eigen
Benign
0.18
Eigen_PC
Benign
-0.011
FATHMM_MKL
Benign
0.32
N
LIST_S2
Pathogenic
0.98
D
M_CAP
Pathogenic
0.98
D
MetaRNN
Pathogenic
0.98
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.5
H
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-3.6
D
REVEL
Uncertain
0.58
Sift
Uncertain
0.024
D
Sift4G
Uncertain
0.021
D
Polyphen
0.92
P
Vest4
0.54
MutPred
0.90
Gain of solvent accessibility (P = 0.005);
MVP
0.95
MPC
2.0
ClinPred
0.90
D
GERP RS
4.3
Varity_R
0.75
gMVP
0.86

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: rs760279009; hg19: chr2-119915502; API