20-15988432-T-G

Variant names:

• chr20-15988432-T-G
• rs775095
• NM_001351661.2:c.1153+1274T>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.1153+1274T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,940 control chromosomes in the GnomAD database, including 12,612 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 0.40 (12612 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.1153+1274T>G		intron_variant	Intron 15 of 17	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.1153+1274T>G		intron_variant	Intron 15 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61022 AN: 151822 Hom.: 12582 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.402 AC: 61112 AN: 151940 Hom.: 12612 Cov.: 32 AF XY: 0.403 AC XY: 29908 AN XY: 74262

African (AFR) AF: 0.468 AC: 19382 AN: 41452

American (AMR) AF: 0.362 AC: 5522 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1361 AN: 3464

East Asian (EAS) AF: 0.491 AC: 2537 AN: 5162

South Asian (SAS) AF: 0.581 AC: 2797 AN: 4812

European-Finnish (FIN) AF: 0.318 AC: 3360 AN: 10578

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24898 AN: 67884

Other (OTH) AF: 0.435 AC: 919 AN: 2112

Alfa AF: 0.381 Hom.: 4305

Bravo AF: 0.404

Asia WGS AF: 0.583 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.2
DANN	Benign	0.48
PhyloP100		2.1
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: rs775095; hg19: chr20-15969077;