chr2-119157702-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182528.4(C1QL2):​c.568C>G​(p.Pro190Ala) 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. 16/22 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. P190T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: C1QL2 NM_182528.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20211291).

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>G	p.Pro190Ala	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>G	p.Pro190Ala	missense	Exon 1 of 2	ENSP00000272520.3	Q7Z5L3
	C1QL2	ENST00000850649.3		c.670C>G	p.Pro224Ala	missense	Exon 1 of 2	ENSP00000642910.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.0061	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.63
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.28
Sift	Benign	0.56	T
Sift4G	Benign	0.11	T
Polyphen		0.044	B
Vest4		0.22
MutPred		0.59		Gain of catalytic residue at P190 (P = 0.0231)
MVP		0.81
MPC		1.0
ClinPred		0.49	T
GERP RS		4.9
Varity_R		0.096
gMVP		0.56
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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;