20-15273405-T-G

Variant names:

• chr20-15273405-T-G
• rs8120608
• NM_001351661.2:c.540+43344T>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.540+43344T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 142,896 control chromosomes in the GnomAD database, including 2,077 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 0.16 (2077 hom., cov: 30)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 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.540+43344T>G		intron	N/A	NP_001338590.1
	MACROD2	NM_001351663.2		c.540+43344T>G		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.540+43344T>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.540+43344T>G		intron	N/A	ENSP00000507484.1
	MACROD2	ENST00000402914.5	TSL:1	c.-166+43344T>G		intron	N/A	ENSP00000385290.1
	MACROD2	ENST00000642719.1		c.540+43344T>G		intron	N/A	ENSP00000496601.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 23517 AN: 142796 Hom.: 2076 Cov.: 30

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0927

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.165 AC: 23525 AN: 142896 Hom.: 2077 Cov.: 30 AF XY: 0.164 AC XY: 11444 AN XY: 69664

African (AFR) AF: 0.0905 AC: 3236 AN: 35750

American (AMR) AF: 0.165 AC: 2393 AN: 14480

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 561 AN: 3412

East Asian (EAS) AF: 0.0934 AC: 472 AN: 5056

South Asian (SAS) AF: 0.178 AC: 790 AN: 4434

European-Finnish (FIN) AF: 0.176 AC: 1773 AN: 10086

Middle Eastern (MID) AF: 0.101 AC: 28 AN: 276

European-Non Finnish (NFE) AF: 0.206 AC: 13736 AN: 66540

Other (OTH) AF: 0.163 AC: 325 AN: 1994

Alfa AF: 0.185 Hom.: 7641

Bravo AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.74
PhyloP100		0.54
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: rs8120608; hg19: chr20-15254051;