dbSNP rs572785251: CREG2:p.Pro163Ser (chr2-101383657-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_153836.4(CREG2):c.487C>T(p.Pro163Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CREG2
NM_153836.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.81

Variant links:

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]

CREG2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREG2	NM_153836.4 link	c.487C>T	p.Pro163Ser	missense_variant	Exon 2 of 4	ENST00000324768.6	NP_722578.1	Q8IUH2
CREG2	XM_017003565.2 link	c.487C>T	p.Pro163Ser	missense_variant	Exon 2 of 3		XP_016859054.2
CREG2	XM_011510777.3 link	c.487C>T	p.Pro163Ser	missense_variant	Exon 2 of 3		XP_011509079.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CREG2	ENST00000324768.6 link	c.487C>T	p.Pro163Ser	missense_variant	Exon 2 of 4	1	NM_153836.4	ENSP00000315203.4	Q8IUH2
CREG2	ENST00000486966.1 link	n.496C>T		non_coding_transcript_exon_variant	Exon 2 of 3	3
CREG2	ENST00000495455.5 link	n.170C>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250284

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135310

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460780

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726658

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.026

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-6.4

REVEL

Uncertain

0.31

Sift

Benign

0.077

Sift4G

Benign

0.075

Polyphen

1.0

Vest4

0.73

MutPred

0.47

Gain of sheet (P = 0.0827);

MVP

0.75

MPC

0.50

ClinPred

0.97

GERP RS

5.0

Varity_R

0.37

gMVP

0.78

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over