rs6135562

Variant names:

• chr20-15826796-T-C
• rs6135562
• NM_001351661.2:c.646-35949T>C

Variant summary

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

The NM_001351661.2(MACROD2):​c.646-35949T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,220 control chromosomes in the GnomAD database, including 2,060 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 0.14 (2060 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	NM_001351661.2	MANE Select	c.646-35949T>C		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.646-35949T>C		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.646-35949T>C		intron	N/A	NP_542407.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.646-35949T>C		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000402914.5	TSL:1	c.-60-35949T>C		intron	N/A	ENSP00000385290.1
	MACROD2	ENST00000642719.1		c.646-35949T>C		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21570 AN: 152102 Hom.: 2052 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.0923

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.142 AC: 21604 AN: 152220 Hom.: 2060 Cov.: 33 AF XY: 0.145 AC XY: 10780 AN XY: 74438

African (AFR) AF: 0.171 AC: 7083 AN: 41538

American (AMR) AF: 0.212 AC: 3245 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2361 AN: 5174

South Asian (SAS) AF: 0.168 AC: 809 AN: 4826

European-Finnish (FIN) AF: 0.0610 AC: 647 AN: 10606

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.0923 AC: 6277 AN: 68010

Other (OTH) AF: 0.169 AC: 356 AN: 2112

Alfa AF: 0.121 Hom.: 2617

Bravo AF: 0.159

Asia WGS AF: 0.273 AC: 943 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.3
DANN	Benign	0.54
PhyloP100		-0.057
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: rs6135562; hg19: chr20-15807441;