chr2-219184665-A-G

Variant names:

• chr2-219184665-A-G
• rs2385393
• NM_024293.6:c.*2036A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024293.6(RETREG2):​c.*2036A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,180 control chromosomes in the GnomAD database, including 68,948 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (68947 hom., cov: 30)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: RETREG2 NM_024293.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510
• Publications: 1 publications found

Genes affected

RETREG2 (HGNC:28450): (reticulophagy regulator family member 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RETREG2	NM_024293.6	c.*2036A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000430297.7	NP_077269.3
RETREG2	NM_001321109.2	c.*2036A>G		3_prime_UTR_variant	Exon 9 of 9		NP_001308038.1
RETREG2	NM_001321110.2	c.*2036A>G		3_prime_UTR_variant	Exon 9 of 9		NP_001308039.1
RETREG2	XM_005246848.4	c.*2036A>G		3_prime_UTR_variant	Exon 10 of 10		XP_005246905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RETREG2	ENST00000430297.7	c.*2036A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_024293.6	ENSP00000395249.2

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144399 AN: 152062 Hom.: 68906 Cov.: 30

Gnomad AFR AF: 0.841

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.941

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.961

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.950 AC: 144499 AN: 152178 Hom.: 68947 Cov.: 30 AF XY: 0.950 AC XY: 70670 AN XY: 74404

African (AFR) AF: 0.841 AC: 34888 AN: 41466

American (AMR) AF: 0.974 AC: 14881 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.980 AC: 3402 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.941 AC: 4545 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10592 AN: 10594

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67776 AN: 68032

Other (OTH) AF: 0.961 AC: 2032 AN: 2114

Alfa AF: 0.972 Hom.: 20827

Bravo AF: 0.944

Asia WGS AF: 0.957 AC: 3330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		-0.051
Mutation Taster		=100/0	polymorphism (auto)

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: rs2385393; hg19: chr2-220049387;