rs743216

Variant names:

• chr20-14338417-A-G
• rs743216
• NM_001351661.2:c.272-155062A>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.272-155062A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,114 control chromosomes in the GnomAD database, including 3,060 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 0.20 (3060 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 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.272-155062A>G		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.272-155062A>G		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.272-155062A>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.272-155062A>G		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000642719.1		c.272-155062A>G		intron	N/A	ENSP00000496601.1
	MACROD2	ENST00000217246.8	TSL:2	c.272-155062A>G		intron	N/A	ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29777 AN: 151994 Hom.: 3061 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.196 AC: 29779 AN: 152114 Hom.: 3060 Cov.: 32 AF XY: 0.198 AC XY: 14710 AN XY: 74366

African (AFR) AF: 0.155 AC: 6429 AN: 41496

American (AMR) AF: 0.163 AC: 2489 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 633 AN: 3472

East Asian (EAS) AF: 0.306 AC: 1579 AN: 5168

South Asian (SAS) AF: 0.270 AC: 1300 AN: 4818

European-Finnish (FIN) AF: 0.247 AC: 2609 AN: 10562

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14033 AN: 68000

Other (OTH) AF: 0.199 AC: 420 AN: 2106

Alfa AF: 0.196 Hom.: 466

Bravo AF: 0.186

Asia WGS AF: 0.297 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.56
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: rs743216; hg19: chr20-14319063;