2-101387267-T-A

Variant names:

• chr2-101387267-T-A
• NM_153836.4:c.191A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153836.4(CREG2):​c.191A>T​(p.Glu64Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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: 1.89

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22414142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CREG2	NM_153836.4	c.191A>T	p.Glu64Val	missense_variant	Exon 1 of 4	ENST00000324768.6	NP_722578.1
CREG2	XM_017003565.2	c.191A>T	p.Glu64Val	missense_variant	Exon 1 of 3		XP_016859054.2
CREG2	XM_011510777.3	c.191A>T	p.Glu64Val	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.191A>T	p.Glu64Val	missense_variant	Exon 1 of 4	1	NM_153836.4	ENSP00000315203.4
CREG2	ENST00000486966.1	n.200A>T		non_coding_transcript_exon_variant	Exon 1 of 3	3
CREG2	ENST00000495455.5	n.-127A>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 23, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.191A>T (p.E64V) alteration is located in exon 1 (coding exon 1) of the CREG2 gene. This alteration results from a A to T substitution at nucleotide position 191, causing the glutamic acid (E) at amino acid position 64 to be replaced by a valine (V). 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	0.30
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	N
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.020
Sift	Benign	0.24	T
Sift4G	Benign	0.50	T
Polyphen		0.028	B
Vest4		0.23
MutPred		0.17		Loss of disorder (P = 0.0055);
MVP		0.57
MPC		2.1
ClinPred		0.47	T
GERP RS		2.8
Varity_R		0.16
gMVP		0.49

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: chr2-102003729;