dbSNP rs1265152968: CREG2:p.Ser73Ile (chr2-101387240-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_153836.4(CREG2):c.218G>T(p.Ser73Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,596 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S73N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CREG2
NM_153836.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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_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.218G>T	p.Ser73Ile	missense	Exon 1 of 4	NP_722578.1	Q8IUH2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CREG2	ENST00000324768.6	TSL:1 MANE Select	c.218G>T	p.Ser73Ile	missense	Exon 1 of 4	ENSP00000315203.4	Q8IUH2
CREG2	ENST00000486966.1	TSL:3	n.227G>T		non_coding_transcript_exon	Exon 1 of 3
CREG2	ENST00000495455.5	TSL:3	n.-100G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1287824

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

633942

African (AFR)

AF:

0.00

AC:

AN:

26584

American (AMR)

AF:

0.00

AC:

AN:

27424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21918

East Asian (EAS)

AF:

0.00

AC:

AN:

28054

South Asian (SAS)

AF:

0.00

AC:

AN:

66550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4680

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1017504

Other (OTH)

AF:

0.00

AC:

AN:

51940

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151596

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000194

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67830

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.1

PhyloP100

3.0

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.4

REVEL

Benign

0.12

Sift

Uncertain

0.0010

Sift4G

Benign

0.16

Polyphen

0.98

Vest4

0.41

MutPred

0.22

Loss of loop (P = 0.0374)

MVP

0.75

MPC

2.5

ClinPred

0.90

GERP RS

4.2

PromoterAI

-0.0082

Neutral

(source)

Varity_R

0.42

gMVP

0.70

Mutation Taster

=69/31

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over