chr20-13995758-G-T

Variant names:

• chr20-13995758-G-T
• rs200598669
• NM_001351661.2:c.-6G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001351661.2(MACROD2):​c.-6G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000811 in 1,232,988 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: MACROD2 NM_001351661.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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]

SEL1L2 (HGNC:15897): (SEL1L2 adaptor subunit of SYVN1 ubiquitin ligase) Predicted to contribute to ubiquitin-protein transferase activity. Predicted to be involved in ubiquitin-dependent ERAD pathway. Predicted to be integral component of membrane. Predicted to be part of Hrd1p ubiquitin ligase ERAD-L complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD2	NM_001351661.2	c.-6G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 18	ENST00000684519.1	NP_001338590.1
MACROD2	NM_001351661.2	c.-6G>T		5_prime_UTR_variant	Exon 1 of 18	ENST00000684519.1	NP_001338590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD2	ENST00000684519	c.-6G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 18		NM_001351661.2	ENSP00000507484.1
MACROD2	ENST00000684519	c.-6G>T		5_prime_UTR_variant	Exon 1 of 18		NM_001351661.2	ENSP00000507484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.11e-7 AC: 1 AN: 1232988 Hom.: 0 Cov.: 36 AF XY: 0.00000164 AC XY: 1 AN XY: 611130

Gnomad4 AFR exome AF: 0.0000373

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200598669; hg19: chr20-13976404;