2-119157977-G-T

Variant names:

• chr2-119157977-G-T
• rs895693195
• NM_182528.4:c.293C>A

Variant summary

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

The NM_182528.4(C1QL2):​c.293C>A​(p.Pro98Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P98L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C1QL2 NM_182528.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84
• 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.293C>A	p.Pro98Gln	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.293C>A	p.Pro98Gln	missense	Exon 1 of 2	ENSP00000272520.3	Q7Z5L3
	C1QL2	ENST00000850649.3		c.395C>A	p.Pro132Gln	missense	Exon 1 of 2	ENSP00000642910.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 112936 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1371896 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 675960

African (AFR) AF: 0.00 AC: 0 AN: 28606

American (AMR) AF: 0.00 AC: 0 AN: 31130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23526

East Asian (EAS) AF: 0.00 AC: 0 AN: 34930

South Asian (SAS) AF: 0.00 AC: 0 AN: 75650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069688

Other (OTH) AF: 0.00 AC: 0 AN: 56700

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.96	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Benign	2.0	M
PhyloP100		7.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.5	N
REVEL	Pathogenic	0.72
Sift	Benign	0.075	T
Sift4G	Benign	0.067	T
Polyphen		0.99	D
Vest4		0.41
MutPred		0.50		Loss of catalytic residue at P98 (P = 0.0361)
MVP		0.96
MPC		2.0
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.15
gMVP		0.35
Mutation Taster		=41/59	disease causing

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

dbSNP: rs895693195; hg19: chr2-119915553;