rs2423846

Positions:

• chr20-14921130-G-A

Variant summary

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

The NM_001351661.2(MACROD2):​c.418+236171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,002 control chromosomes in the GnomAD database, including 20,527 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 0.51 (20527 hom., cov: 33)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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-AS1 (HGNC:37193): (MACROD2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MACROD2	NM_001351661.2	c.418+236171G>A		intron_variant		ENST00000684519.1
MACROD2-AS1	NR_110318.1	n.144+8245C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+236171G>A		intron_variant			NM_001351661.2	P2
MACROD2-AS1	ENST00000664409.1	n.154+8245C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78105 AN: 151882 Hom.: 20504 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.514 AC: 78176 AN: 152002 Hom.: 20527 Cov.: 33 AF XY: 0.515 AC XY: 38255 AN XY: 74288

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.501

Alfa AF: 0.544 Hom.: 47269

Bravo AF: 0.510

Asia WGS AF: 0.644 AC: 2236 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.50

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: rs2423846; hg19: chr20-14901776;