chr20-14725242-A-G

Position:

• chr20-14725242-A-G

Variant summary

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

The NM_001351661.2(MACROD2):​c.418+40283A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,020 control chromosomes in the GnomAD database, including 15,951 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 0.45 (15951 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.418+40283A>G		intron_variant		ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.418+40283A>G		intron_variant			NP_001338592.1
MACROD2	NM_080676.6	c.418+40283A>G		intron_variant			NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+40283A>G		intron_variant			NM_001351661.2	ENSP00000507484	P2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68258 AN: 151902 Hom.: 15946 Cov.: 31

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.449 AC: 68278 AN: 152020 Hom.: 15951 Cov.: 31 AF XY: 0.448 AC XY: 33266 AN XY: 74322

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.452

Alfa AF: 0.484 Hom.: 35821

Bravo AF: 0.431

Asia WGS AF: 0.289 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.64

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: rs6079540; hg19: chr20-14705888;