2-101387138-C-G

Variant names:

• chr2-101387138-C-G
• rs1420743598
• NM_153836.4:c.320G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153836.4(CREG2):​c.320G>C​(p.Arg107Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,098,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. R107L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: CREG2 NM_153836.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33122683).

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.320G>C	p.Arg107Pro	missense	Exon 1 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.320G>C	p.Arg107Pro	missense	Exon 1 of 4	ENSP00000315203.4	Q8IUH2
	CREG2	ENST00000486966.1	TSL:3	n.329G>C		non_coding_transcript_exon	Exon 1 of 3
	CREG2	ENST00000495455.5	TSL:3	n.3G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1098504 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 522060

African (AFR) AF: 0.00 AC: 0 AN: 22856

American (AMR) AF: 0.00 AC: 0 AN: 8348

Ashkenazi Jewish (ASJ) AF: 0.0000691 AC: 1 AN: 14462

East Asian (EAS) AF: 0.00 AC: 0 AN: 26466

South Asian (SAS) AF: 0.00 AC: 0 AN: 25000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2962

European-Non Finnish (NFE) AF: 0.00000215 AC: 2 AN: 930080

Other (OTH) AF: 0.0000226 AC: 1 AN: 44246

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.097	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.86	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.025
Sift	Benign	0.030	D
Sift4G	Uncertain	0.060	T
Polyphen		0.068	B
Vest4		0.25
MutPred		0.38		Loss of sheet (P = 0.0181)
MVP		0.59
MPC		1.6
ClinPred		0.75	D
GERP RS		0.99
PromoterAI		-0.033	Neutral
Varity_R		0.63
gMVP		0.54
Mutation Taster		=70/30	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: rs1420743598; hg19: chr2-102003600;