20-14589296-G-T

Position:

• chr20-14589296-G-T

Variant summary

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

The NM_001351661.2(MACROD2):​c.302-95547G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,000 control chromosomes in the GnomAD database, including 32,791 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 0.64 (32791 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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-IT1 (HGNC:16201): (MACROD2 intronic transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.302-95547G>T		intron_variant		ENST00000684519.1
MACROD2-IT1	NR_104193.2	n.46-32470G>T		intron_variant, non_coding_transcript_variant
MACROD2	NM_001351663.2	c.302-95547G>T		intron_variant
MACROD2	NM_080676.6	c.302-95547G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.302-95547G>T		intron_variant			NM_001351661.2	P2
MACROD2-IT1	ENST00000448536.1	n.46-32470G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97336 AN: 151882 Hom.: 32791 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.724

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.640 AC: 97351 AN: 152000 Hom.: 32791 Cov.: 33 AF XY: 0.646 AC XY: 48008 AN XY: 74284

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.686

Alfa AF: 0.687 Hom.: 15329

Bravo AF: 0.638

Asia WGS AF: 0.821 AC: 2828 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.097
DANN	Benign	0.71

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: rs6079501; hg19: chr20-14569942;