chr11-126306583-C-CTGGGGA

Variant names:

• chr11-126306583-C-CTGGGGA
• rs201095573
• NM_014026.6:c.225_230dupGGATGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BS1 BS2

The NM_014026.6(DCPS):​c.225_230dupGGATGG​(p.Gly77_Glu78insAspGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,608,582 control chromosomes in the GnomAD database, including 384 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 31)
  • Exomes 𝑓: 0.018 (364 hom.)
• Consequence: DCPS NM_014026.6 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.419

Genes affected

DCPS (HGNC:29812): (decapping enzyme, scavenger) This gene encodes a member of the histidine triad family of pyrophosphatases that removes short mRNA fragments containing the 5′ mRNA cap structure, which appear in the 3′ → 5′ mRNA decay pathway, following deadenylation and exosome-mediated turnover. This enzyme hydrolyzes the triphosphate linkage of the cap structure (7-methylguanosine nucleoside triphosphate) to yield 7-methylguanosine monophosphate and nucleoside diphosphate. It protects the cell from the potentially toxic accumulation of these short, capped mRNA fragments, and regulates the activity of other cap-binding proteins, which are inhibited by their accumulation. It also acts as a transcript-specific modulator of pre-mRNA splicing and microRNA turnover. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_014026.6.
• BP6: Variant 11-126306583-C-CTGGGGA is Benign according to our data. Variant chr11-126306583-C-CTGGGGA is described in ClinVar as [Benign]. Clinvar id is 3068672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0123 (1875/152182) while in subpopulation SAS AF = 0.0357 (172/4814). AF 95% confidence interval is 0.0314. There are 20 homozygotes in GnomAd4. There are 902 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCPS	NM_014026.6	c.225_230dupGGATGG	p.Gly77_Glu78insAspGly	disruptive_inframe_insertion	Exon 2 of 6	ENST00000263579.5	NP_054745.1
DCPS	NM_001350236.2	c.246_251dupGGATGG	p.Gly84_Glu85insAspGly	disruptive_inframe_insertion	Exon 2 of 6		NP_001337165.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCPS	ENST00000263579.5	c.225_230dupGGATGG	p.Gly77_Glu78insAspGly	disruptive_inframe_insertion	Exon 2 of 6	1	NM_014026.6	ENSP00000263579.4

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1876 AN: 152064 Hom.: 20 Cov.: 31

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00544

Gnomad ASJ AF: 0.0309

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0353

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.0173 AC: 4283 AN: 247900 AF XY: 0.0190

Gnomad AFR exome AF: 0.00229

Gnomad AMR exome AF: 0.00552

Gnomad ASJ exome AF: 0.0314

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0125

Gnomad NFE exome AF: 0.0196

Gnomad OTH exome AF: 0.0180

GnomAD4 exome AF: 0.0183 AC: 26676 AN: 1456400 Hom.: 364 Cov.: 30 AF XY: 0.0192 AC XY: 13923 AN XY: 723458

Gnomad4 AFR exome AF: 0.00222 AC: 74 AN: 33404

Gnomad4 AMR exome AF: 0.00541 AC: 241 AN: 44576

Gnomad4 ASJ exome AF: 0.0305 AC: 796 AN: 26078

Gnomad4 EAS exome AF: 0.000127 AC: 5 AN: 39480

Gnomad4 SAS exome AF: 0.0411 AC: 3527 AN: 85882

Gnomad4 FIN exome AF: 0.0144 AC: 769 AN: 53342

Gnomad4 NFE exome AF: 0.0180 AC: 19991 AN: 1108108

Gnomad4 Remaining exome AF: 0.0192 AC: 1153 AN: 60112

GnomAD4 genome AF: 0.0123 AC: 1875 AN: 152182 Hom.: 20 Cov.: 31 AF XY: 0.0121 AC XY: 902 AN XY: 74406

Gnomad4 AFR AF: 0.00272 AC: 0.00272132 AN: 0.00272132

Gnomad4 AMR AF: 0.00543 AC: 0.00542838 AN: 0.00542838

Gnomad4 ASJ AF: 0.0309 AC: 0.0308535 AN: 0.0308535

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.0357 AC: 0.0357291 AN: 0.0357291

Gnomad4 FIN AF: 0.0121 AC: 0.0120892 AN: 0.0120892

Gnomad4 NFE AF: 0.0182 AC: 0.0182179 AN: 0.0182179

Gnomad4 OTH AF: 0.0123 AC: 0.0122873 AN: 0.0122873

Alfa AF: 0.0186 Hom.: 20

Asia WGS AF: 0.0150 AC: 51 AN: 3478

EpiCase AF: 0.0189

EpiControl AF: 0.0180

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Al-Raqad syndrome Benign:1

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

South Asian population allele frequency is 3.731% (rs201095573,1185/30256 alleles, 32 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=75/25	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201095573; hg19: chr11-126176478;