20-15140098-A-G

Variant names:

• chr20-15140098-A-G
• rs11087123
• NM_001351661.2:c.419-89842A>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.419-89842A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,150 control chromosomes in the GnomAD database, including 5,381 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 0.26 (5381 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.419-89842A>G		intron_variant	Intron 5 of 17	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.419-89842A>G		intron_variant	Intron 5 of 17		NP_001338592.1
MACROD2	NM_080676.6	c.419-89842A>G		intron_variant	Intron 5 of 16		NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.419-89842A>G		intron_variant	Intron 5 of 17		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000642719.1	c.419-89842A>G		intron_variant	Intron 5 of 17			ENSP00000496601.1
MACROD2	ENST00000217246.8	c.419-89842A>G		intron_variant	Intron 5 of 16	2		ENSP00000217246.4

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39560 AN: 152032 Hom.: 5379 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.260 AC: 39578 AN: 152150 Hom.: 5381 Cov.: 33 AF XY: 0.261 AC XY: 19391 AN XY: 74398

African (AFR) AF: 0.216 AC: 8947 AN: 41516

American (AMR) AF: 0.238 AC: 3643 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3464

East Asian (EAS) AF: 0.391 AC: 2014 AN: 5154

South Asian (SAS) AF: 0.437 AC: 2111 AN: 4826

European-Finnish (FIN) AF: 0.218 AC: 2313 AN: 10600

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18451 AN: 67978

Other (OTH) AF: 0.292 AC: 617 AN: 2112

Alfa AF: 0.271 Hom.: 14234

Bravo AF: 0.255

Asia WGS AF: 0.432 AC: 1500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		2.0
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: rs11087123; hg19: chr20-15120744;