20-15897446-T-C

Variant names:

• chr20-15897446-T-C
• rs717145
• NM_001351661.2:c.775+11635T>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.775+11635T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,976 control chromosomes in the GnomAD database, including 31,925 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 0.62 (31925 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.948
• 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]

ENSG00000286546 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.775+11635T>C		intron_variant	Intron 10 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.775+11635T>C		intron_variant	Intron 10 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93668 AN: 151858 Hom.: 31919 Cov.: 31

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.616 AC: 93678 AN: 151976 Hom.: 31925 Cov.: 31 AF XY: 0.618 AC XY: 45930 AN XY: 74270

African (AFR) AF: 0.308 AC: 12766 AN: 41456

American (AMR) AF: 0.637 AC: 9733 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2542 AN: 3468

East Asian (EAS) AF: 0.578 AC: 2986 AN: 5164

South Asian (SAS) AF: 0.619 AC: 2976 AN: 4804

European-Finnish (FIN) AF: 0.779 AC: 8221 AN: 10550

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52250 AN: 67940

Other (OTH) AF: 0.635 AC: 1342 AN: 2112

Alfa AF: 0.682 Hom.: 7308

Bravo AF: 0.592

Asia WGS AF: 0.579 AC: 2012 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.7
DANN	Benign	0.66
PhyloP100		0.95
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: rs717145; hg19: chr20-15878091;