chr2-101387144-G-C

Variant names:

• chr2-101387144-G-C
• rs1363983140
• NM_153836.4:c.314C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153836.4(CREG2):​c.314C>G​(p.Ser105Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CREG2 NM_153836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.46

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

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, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREG2	NM_153836.4	c.314C>G	p.Ser105Cys	missense_variant	Exon 1 of 4	ENST00000324768.6	NP_722578.1
CREG2	XM_017003565.2	c.314C>G	p.Ser105Cys	missense_variant	Exon 1 of 3		XP_016859054.2
CREG2	XM_011510777.3	c.314C>G	p.Ser105Cys	missense_variant	Exon 1 of 3		XP_011509079.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CREG2	ENST00000324768.6	c.314C>G	p.Ser105Cys	missense_variant	Exon 1 of 4	1	NM_153836.4	ENSP00000315203.4
CREG2	ENST00000486966.1	n.323C>G		non_coding_transcript_exon_variant	Exon 1 of 3	3
CREG2	ENST00000495455.5	n.-4C>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.314C>G (p.S105C) alteration is located in exon 1 (coding exon 1) of the CREG2 gene. This alteration results from a C to G substitution at nucleotide position 314, causing the serine (S) at amino acid position 105 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.26
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.29		Loss of phosphorylation at S105 (P = 0.0077);
MVP		0.86
MPC		2.3
ClinPred		0.96	D
GERP RS		4.1
Varity_R		0.30
gMVP		0.67

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

Other links and lift over

dbSNP: rs1363983140; hg19: chr2-102003606;