rs2876409

Variant names:

• chr20-15486430-G-A
• rs2876409
• NM_001351661.2:c.572-13344G>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.572-13344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,102 control chromosomes in the GnomAD database, including 8,174 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 0.31 (8174 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 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.572-13344G>A		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.572-13344G>A		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.572-13344G>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.572-13344G>A		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000402914.5	TSL:1	c.-134-13344G>A		intron	N/A	ENSP00000385290.1
	MACROD2	ENST00000642719.1		c.572-13344G>A		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47231 AN: 151984 Hom.: 8164 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.311 AC: 47238 AN: 152102 Hom.: 8174 Cov.: 32 AF XY: 0.312 AC XY: 23224 AN XY: 74336

African (AFR) AF: 0.159 AC: 6586 AN: 41526

American (AMR) AF: 0.301 AC: 4591 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3466

East Asian (EAS) AF: 0.420 AC: 2168 AN: 5156

South Asian (SAS) AF: 0.298 AC: 1438 AN: 4824

European-Finnish (FIN) AF: 0.425 AC: 4492 AN: 10560

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

European-Non Finnish (NFE) AF: 0.378 AC: 25706 AN: 67978

Other (OTH) AF: 0.307 AC: 650 AN: 2116

Alfa AF: 0.353 Hom.: 16779

Bravo AF: 0.297

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.39
PhyloP100		-0.57
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: rs2876409; hg19: chr20-15467075; COSMIC: COSV54041952;