chr2-119158040-G-A

Variant names:

• chr2-119158040-G-A
• NM_182528.4:c.230C>T

Variant summary

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

The NM_182528.4(C1QL2):​c.230C>T​(p.Pro77Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000653 in 1,377,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: C1QL2 NM_182528.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• 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.230C>T	p.Pro77Leu	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.230C>T	p.Pro77Leu	missense	Exon 1 of 2	ENSP00000272520.3	Q7Z5L3
	C1QL2	ENST00000850649.3		c.332C>T	p.Pro111Leu	missense	Exon 1 of 2	ENSP00000642910.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000653 AC: 9 AN: 1377734 Hom.: 0 Cov.: 34 AF XY: 0.00000441 AC XY: 3 AN XY: 679618

African (AFR) AF: 0.00 AC: 0 AN: 28092

American (AMR) AF: 0.00 AC: 0 AN: 33536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24160

East Asian (EAS) AF: 0.00 AC: 0 AN: 33504

South Asian (SAS) AF: 0.00 AC: 0 AN: 77646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5294

European-Non Finnish (NFE) AF: 0.00000841 AC: 9 AN: 1070770

Other (OTH) AF: 0.00 AC: 0 AN: 57042

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	0.12
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	0.0029
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	0.52	D
MutationAssessor	Benign	1.7	L
PhyloP100		1.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.36
Sift	Benign	0.13	T
Sift4G	Benign	0.11	T
Polyphen		0.19	B
Vest4		0.13
MutPred		0.41		Gain of catalytic residue at P77 (P = 0.0569)
MVP		0.93
MPC		1.0
ClinPred		0.76	D
GERP RS		4.3
Varity_R		0.23
gMVP		0.22
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

hg19: chr2-119915616; COSMIC: COSV55606220;