2-101383657-G-T

Variant names:

• chr2-101383657-G-T
• rs572785251
• NM_153836.4:c.487C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153836.4(CREG2):​c.487C>A​(p.Pro163Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. P163A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CREG2 NM_153836.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81
• Publications: 0 publications found

Genes affected

CREG2 (HGNC:14272): (cellular repressor of E1A stimulated genes 2) Predicted to be located in Golgi apparatus and endoplasmic reticulum. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153836.4. 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
	CREG2	NM_153836.4	MANE Select	c.487C>A	p.Pro163Thr	missense	Exon 2 of 4	NP_722578.1	Q8IUH2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREG2	ENST00000324768.6	TSL:1 MANE Select	c.487C>A	p.Pro163Thr	missense	Exon 2 of 4	ENSP00000315203.4	Q8IUH2
	CREG2	ENST00000486966.1	TSL:3	n.496C>A		non_coding_transcript_exon	Exon 2 of 3
	CREG2	ENST00000495455.5	TSL:3	n.170C>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.16
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.26
Sift	Benign	0.098	T
Sift4G	Benign	0.076	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.49		Gain of catalytic residue at P163 (P = 0.0763)
MVP		0.74
MPC		0.51
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.44
gMVP		0.76
Mutation Taster		=46/54	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: rs572785251; hg19: chr2-102000119; COSMIC: COSV100240618;