NM_001351661.2:c.541-88769A>G

Variant names:

• chr20-15342636-A-G
• rs2423942
• NM_001351661.2:c.541-88769A>G

Variant summary

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

The NM_001351661.2(MACROD2):​c.541-88769A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,986 control chromosomes in the GnomAD database, including 29,398 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 0.62 (29398 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 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.541-88769A>G		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.541-88769A>G		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.541-88769A>G		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.541-88769A>G		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000402914.5	TSL:1	c.-165-88769A>G		intron	N/A	ENSP00000385290.1
	MACROD2	ENST00000642719.1		c.541-88769A>G		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94275 AN: 151868 Hom.: 29372 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.621 AC: 94351 AN: 151986 Hom.: 29398 Cov.: 32 AF XY: 0.621 AC XY: 46153 AN XY: 74266

African (AFR) AF: 0.637 AC: 26373 AN: 41430

American (AMR) AF: 0.667 AC: 10192 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2150 AN: 3470

East Asian (EAS) AF: 0.753 AC: 3888 AN: 5162

South Asian (SAS) AF: 0.642 AC: 3090 AN: 4812

European-Finnish (FIN) AF: 0.539 AC: 5686 AN: 10556

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.603 AC: 40951 AN: 67966

Other (OTH) AF: 0.625 AC: 1322 AN: 2114

Alfa AF: 0.616 Hom.: 11001

Bravo AF: 0.636

Asia WGS AF: 0.674 AC: 2345 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.56
PhyloP100		0.17
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: rs2423942; hg19: chr20-15323282;