20-14378280-A-G

Position:

• chr20-14378280-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.272-115199A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 152,272 control chromosomes in the GnomAD database, including 73,437 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 0.98 (73437 hom., cov: 31)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

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]

MACROD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.272-115199A>G		intron_variant		ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.272-115199A>G		intron_variant			NP_001338592.1
MACROD2	NM_080676.6	c.272-115199A>G		intron_variant			NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.272-115199A>G		intron_variant			NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.982 AC: 149430 AN: 152154 Hom.: 73378 Cov.: 31

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.975

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

GnomAD4 genome AF: 0.982 AC: 149548 AN: 152272 Hom.: 73437 Cov.: 31 AF XY: 0.982 AC XY: 73134 AN XY: 74458

Gnomad4 AFR AF: 0.984

Gnomad4 AMR AF: 0.973

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.994

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.980

Gnomad4 OTH AF: 0.975

Alfa AF: 0.981 Hom.: 9326

Bravo AF: 0.980

Asia WGS AF: 0.994 AC: 3457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.52

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: rs204652; hg19: chr20-14358926;