chr20-14436551-G-T

Variant names:

• chr20-14436551-G-T
• rs8116105
• NM_001351661.2:c.272-56928G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351661.2(MACROD2):​c.272-56928G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,954 control chromosomes in the GnomAD database, including 7,712 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 0.30 (7712 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.272-56928G>T		intron_variant	Intron 3 of 17	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351663.2	c.272-56928G>T		intron_variant	Intron 3 of 17		NP_001338592.1
MACROD2	NM_080676.6	c.272-56928G>T		intron_variant	Intron 3 of 16		NP_542407.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.272-56928G>T		intron_variant	Intron 3 of 17		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44980 AN: 151836 Hom.: 7713 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.296 AC: 44982 AN: 151954 Hom.: 7712 Cov.: 33 AF XY: 0.301 AC XY: 22340 AN XY: 74262

African (AFR) AF: 0.134 AC: 5565 AN: 41450

American (AMR) AF: 0.365 AC: 5567 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1487 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2631 AN: 5156

South Asian (SAS) AF: 0.582 AC: 2805 AN: 4816

European-Finnish (FIN) AF: 0.265 AC: 2797 AN: 10536

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23028 AN: 67948

Other (OTH) AF: 0.323 AC: 684 AN: 2116

Alfa AF: 0.236 Hom.: 865

Bravo AF: 0.293

Asia WGS AF: 0.507 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.089
DANN	Benign	0.64
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8116105; hg19: chr20-14417197;