20-15273405-T-G

Position:

• chr20-15273405-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.540+43344T>G		intron_variant		ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.540+43344T>G		intron_variant			NM_001351661.2	ENSP00000507484	P2
MACROD2	ENST00000402914.5	c.-166+43344T>G		intron_variant		1		ENSP00000385290
MACROD2	ENST00000217246.8	c.540+43344T>G		intron_variant		2		ENSP00000217246	A2
MACROD2	ENST00000642719.1	c.540+43344T>G		intron_variant				ENSP00000496601	A2

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

Gnomad4 AFR AF: 0.0905

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0934

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.163

Alfa AF: 0.187 Hom.: 5429

Bravo AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs8120608; hg19: chr20-15254051;