2-101387120-G-T

Variant names:

• chr2-101387120-G-T
• rs1381504517
• NM_153836.4:c.338C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153836.4(CREG2):​c.338C>A​(p.Thr113Lys) 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. 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. T113M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CREG2 NM_153836.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06690061).

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.338C>A	p.Thr113Lys	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.338C>A	p.Thr113Lys	missense	Exon 1 of 4	ENSP00000315203.4	Q8IUH2
	CREG2	ENST00000486966.1	TSL:3	n.347C>A		non_coding_transcript_exon	Exon 1 of 3
	CREG2	ENST00000495455.5	TSL:3	n.21C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1092352 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 518076

African (AFR) AF: 0.00 AC: 0 AN: 22864

American (AMR) AF: 0.00 AC: 0 AN: 8342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14410

East Asian (EAS) AF: 0.00 AC: 0 AN: 26522

South Asian (SAS) AF: 0.00 AC: 0 AN: 23076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2946

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 927452

Other (OTH) AF: 0.00 AC: 0 AN: 44076

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.0
DANN	Benign	0.72
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.81	N
PhyloP100		0.98
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.040
Sift	Benign	0.28	T
Sift4G	Benign	0.35	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.27		Gain of MoRF binding (P = 0.0318)
MVP		0.099
MPC		1.4
ClinPred		0.068	T
GERP RS		1.4
PromoterAI		0.056	Neutral
Varity_R		0.071
gMVP		0.40
Mutation Taster		=100/0	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: rs1381504517; hg19: chr2-102003582;