20-15921985-C-T

Variant names:

• chr20-15921985-C-T
• rs6034328
• NM_001351661.2:c.776-11291C>T

Variant summary

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

The ENST00000684519.1(MACROD2):​c.776-11291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,226 control chromosomes in the GnomAD database, including 55,891 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 0.85 (55891 hom., cov: 33)
• Consequence: MACROD2 ENST00000684519.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 2 publications found

Genes affected

MACROD2 (HGNC:16126): (mono-ADP ribosylhydrolase 2) The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

ENSG00000286546 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000684519.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	NM_001351661.2	MANE Select	c.776-11291C>T		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.776-11291C>T		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.776-11291C>T		intron	N/A	NP_542407.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.776-11291C>T		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000402914.5	TSL:1	c.71-11291C>T		intron	N/A	ENSP00000385290.1
	MACROD2	ENST00000642719.1		c.860-11291C>T		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128990 AN: 152108 Hom.: 55868 Cov.: 33

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.882

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.845

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.848 AC: 129069 AN: 152226 Hom.: 55891 Cov.: 33 AF XY: 0.848 AC XY: 63134 AN XY: 74440

African (AFR) AF: 0.672 AC: 27882 AN: 41492

American (AMR) AF: 0.819 AC: 12532 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3053 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3666 AN: 5162

South Asian (SAS) AF: 0.895 AC: 4314 AN: 4820

European-Finnish (FIN) AF: 0.947 AC: 10060 AN: 10624

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.951 AC: 64708 AN: 68026

Other (OTH) AF: 0.847 AC: 1792 AN: 2116

Alfa AF: 0.904 Hom.: 81320

Bravo AF: 0.826

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.50
PhyloP100		-0.0010
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: rs6034328; hg19: chr20-15902630;