20-15455357-G-A

Variant names:

• chr20-15455357-G-A
• rs6074898
• NM_001351661.2:c.571+23922G>A

Variant summary

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

The NM_001351661.2(MACROD2):​c.571+23922G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,166 control chromosomes in the GnomAD database, including 55,407 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 (55407 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63
• Publications: 5 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351661.2. 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.571+23922G>A		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.571+23922G>A		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.571+23922G>A		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.571+23922G>A		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000402914.5	TSL:1	c.-135+23922G>A		intron	N/A	ENSP00000385290.1
	MACROD2	ENST00000642719.1		c.571+23922G>A		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129577 AN: 152048 Hom.: 55370 Cov.: 33

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.870

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.852 AC: 129671 AN: 152166 Hom.: 55407 Cov.: 33 AF XY: 0.851 AC XY: 63301 AN XY: 74362

African (AFR) AF: 0.906 AC: 37622 AN: 41524

American (AMR) AF: 0.882 AC: 13477 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2868 AN: 3472

East Asian (EAS) AF: 0.954 AC: 4927 AN: 5164

South Asian (SAS) AF: 0.869 AC: 4197 AN: 4830

European-Finnish (FIN) AF: 0.798 AC: 8450 AN: 10588

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55341 AN: 67984

Other (OTH) AF: 0.858 AC: 1815 AN: 2116

Alfa AF: 0.831 Hom.: 160812

Bravo AF: 0.860

Asia WGS AF: 0.889 AC: 3091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	14
DANN	Benign	0.55
PhyloP100		2.6
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: rs6074898; hg19: chr20-15436002;