rs14135

Positions:

• chr20-14884510-T-C

Variant summary

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

The NM_001351661.2(MACROD2):​c.418+199551T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,046 control chromosomes in the GnomAD database, including 5,286 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 0.25 (5282 hom., cov: 32)
  • Exomes 𝑓: 0.37 (4 hom.)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.418+199551T>C		intron_variant		ENST00000684519.1	NP_001338590.1
MACROD2-AS1	NR_110318.1	n.229A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519.1	c.418+199551T>C		intron_variant			NM_001351661.2	ENSP00000507484	P2
MACROD2-AS1	ENST00000664409.1	n.239A>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38160 AN: 151872 Hom.: 5277 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.370 AC: 20 AN: 54 Hom.: 4 Cov.: 0 AF XY: 0.333 AC XY: 16 AN XY: 48

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.251 AC: 38174 AN: 151992 Hom.: 5282 Cov.: 32 AF XY: 0.249 AC XY: 18473 AN XY: 74270

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.228

Alfa AF: 0.215 Hom.: 6232

Bravo AF: 0.249

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.64

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: rs14135; hg19: chr20-14865156;