20-16022761-T-C

Position:

• chr20-16022761-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351661.2(MACROD2):​c.1154-18440T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,072 control chromosomes in the GnomAD database, including 6,126 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 0.27 (6126 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.1154-18440T>C		intron_variant		ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.1154-18440T>C		intron_variant			NM_001351661.2	ENSP00000507484	P2

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41208 AN: 151954 Hom.: 6124 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0740

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.271 AC: 41242 AN: 152072 Hom.: 6126 Cov.: 32 AF XY: 0.277 AC XY: 20560 AN XY: 74326

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0746

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.271

Alfa AF: 0.312 Hom.: 3841

Bravo AF: 0.257

Asia WGS AF: 0.226 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.9
DANN	Benign	0.57

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: rs6080100; hg19: chr20-16003406;