NM_182528.4:c.238G>T

Variant names:

• chr2-119158032-C-A
• NM_182528.4:c.238G>T

Variant summary

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

The NM_182528.4(C1QL2):​c.238G>T​(p.Asp80Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,376,090 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: 7.3e-7 (0 hom.)
• Consequence: C1QL2 NM_182528.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48
• 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.238G>T	p.Asp80Tyr	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.238G>T	p.Asp80Tyr	missense	Exon 1 of 2	ENSP00000272520.3	Q7Z5L3
	C1QL2	ENST00000850649.3		c.340G>T	p.Asp114Tyr	missense	Exon 1 of 2	ENSP00000642910.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1376090 Hom.: 0 Cov.: 34 AF XY: 0.00000147 AC XY: 1 AN XY: 678740

African (AFR) AF: 0.00 AC: 0 AN: 27924

American (AMR) AF: 0.00 AC: 0 AN: 33278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24106

East Asian (EAS) AF: 0.0000299 AC: 1 AN: 33416

South Asian (SAS) AF: 0.00 AC: 0 AN: 77400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5160

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070260

Other (OTH) AF: 0.00 AC: 0 AN: 56936

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	Uncertain	0.47
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	1.0	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Benign	1.6	L
PhyloP100		2.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.043	D
Polyphen		0.88	P
Vest4		0.15
MutPred		0.35		Gain of phosphorylation at D80 (P = 0.0215)
MVP		0.91
MPC		1.5
ClinPred		0.89	D
GERP RS		3.4
Varity_R		0.18
gMVP		0.42
Mutation Taster		=63/37	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: chr2-119915608;