2-101387289-C-A

Variant names:

• chr2-101387289-C-A
• rs1259771979
• NM_153836.4:c.169G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153836.4(CREG2):​c.169G>T​(p.Glu57*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000749 in 1,335,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: CREG2 NM_153836.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• 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 2 ACMG points.

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

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.169G>T	p.Glu57*	stop_gained	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.169G>T	p.Glu57*	stop_gained	Exon 1 of 4	ENSP00000315203.4	Q8IUH2
	CREG2	ENST00000486966.1	TSL:3	n.178G>T		non_coding_transcript_exon	Exon 1 of 3
	CREG2	ENST00000495455.5	TSL:3	n.-149G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1335356 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 659358

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27678

American (AMR) AF: 0.00 AC: 0 AN: 31272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23148

East Asian (EAS) AF: 0.0000330 AC: 1 AN: 30336

South Asian (SAS) AF: 0.00 AC: 0 AN: 72670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5388

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1043788

Other (OTH) AF: 0.00 AC: 0 AN: 54462

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	0.86
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Benign	0.71	D
PhyloP100		4.4
Vest4		0.10
GERP RS		4.1
PromoterAI		-0.013	Neutral
Mutation Taster		=28/172	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1259771979; hg19: chr2-102003751;