2-101383657-G-A

Variant names:

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

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>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
• 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, 0.782

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>T	p.Pro163Ser	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>T	p.Pro163Ser	missense	Exon 2 of 4	ENSP00000315203.4	Q8IUH2
	CREG2	ENST00000486966.1	TSL:3	n.496C>T		non_coding_transcript_exon	Exon 2 of 3
	CREG2	ENST00000495455.5	TSL:3	n.170C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250284 AF XY: 0.00000739

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: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460780 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726658

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111494

Other (OTH) AF: 0.0000166 AC: 1 AN: 60350

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.8
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.31
Sift	Benign	0.077	T
Sift4G	Benign	0.075	T
Polyphen		1.0	D
Vest4		0.73
MutPred		0.47		Gain of sheet (P = 0.0827)
MVP		0.75
MPC		0.50
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.37
gMVP		0.78
Mutation Taster		=54/46	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

dbSNP: rs572785251; hg19: chr2-102000119;