rs6079536

chr20-14716236-A-Cchr20-14716236-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001351661.2(MACROD2):c.418+31277A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,994 control chromosomes in the GnomAD database, including 21,012 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 0.52 (21012 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.418+31277A>C		intron_variant		ENST00000684519.1
MACROD2	NM_001351663.2	c.418+31277A>C		intron_variant
MACROD2	NM_080676.6	c.418+31277A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+31277A>C		intron_variant			NM_001351661.2	P2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79048 AN: 151876 Hom.: 21003 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.520 AC: 79075 AN: 151994 Hom.: 21012 Cov.: 32 AF XY: 0.516 AC XY: 38356 AN XY: 74278

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.522

Alfa AF: 0.503 Hom.: 3566

Bravo AF: 0.507

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	14
Dann	Benign	0.93

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: rs6079536; hg19: chr20-14696882; COSMIC: COSV53973943;