chr2-119157702-G-T

Variant names:

• chr2-119157702-G-T
• rs753735785
• NM_182528.4:c.568C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182528.4(C1QL2):​c.568C>A​(p.Pro190Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: C1QL2 NM_182528.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182528.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QL2	NM_182528.4	MANE Select	c.568C>A	p.Pro190Thr	missense	Exon 1 of 2	NP_872334.2	Q7Z5L3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QL2	ENST00000272520.4	TSL:1 MANE Select	c.568C>A	p.Pro190Thr	missense	Exon 1 of 2	ENSP00000272520.3	Q7Z5L3
	C1QL2	ENST00000850649.3		c.670C>A	p.Pro224Thr	missense	Exon 1 of 2	ENSP00000642910.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250764 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.51
Sift	Benign	0.053	T
Sift4G	Benign	0.073	T
Polyphen		0.89	P
Vest4		0.51
MutPred		0.59		Gain of catalytic residue at P190 (P = 0.0372)
MVP		0.89
MPC		2.1
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.24
gMVP		0.69
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs753735785; hg19: chr2-119915278;