2-101387240-C-T

Variant names:

• chr2-101387240-C-T
• NM_153836.4:c.218G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153836.4(CREG2):​c.218G>A​(p.Ser73Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000777 in 1,287,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: CREG2 NM_153836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.00

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREG2	NM_153836.4	c.218G>A	p.Ser73Asn	missense_variant	Exon 1 of 4	ENST00000324768.6	NP_722578.1
CREG2	XM_017003565.2	c.218G>A	p.Ser73Asn	missense_variant	Exon 1 of 3		XP_016859054.2
CREG2	XM_011510777.3	c.218G>A	p.Ser73Asn	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.218G>A	p.Ser73Asn	missense_variant	Exon 1 of 4	1	NM_153836.4	ENSP00000315203.4
CREG2	ENST00000486966.1	n.227G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3
CREG2	ENST00000495455.5	n.-100G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.77e-7 AC: 1 AN: 1287824 Hom.: 0 Cov.: 33 AF XY: 0.00000158 AC XY: 1 AN XY: 633942

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: 0.0000150

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.218G>A (p.S73N) alteration is located in exon 1 (coding exon 1) of the CREG2 gene. This alteration results from a G to A substitution at nucleotide position 218, causing the serine (S) at amino acid position 73 to be replaced by an asparagine (N). 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	Benign	0.20
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.084
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.032	D
Polyphen		0.98	D
Vest4		0.34
MutPred		0.20		Gain of catalytic residue at S73 (P = 0.0078);
MVP		0.65
MPC		2.1
ClinPred		0.83	D
GERP RS		4.2
Varity_R		0.40
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-102003702;