chr11-3808066-CCGG-C

Variant names:

• chr11-3808066-CCGG-C
• rs75108073
• ENST00000300730.10:c.140-227_140-225delCGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001346403.1(PGAP2):​c.-53_-51delCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,423,458 control chromosomes in the GnomAD database, including 10,405 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (850 hom., cov: 28)
  • Exomes 𝑓: 0.12 (9555 hom.)
• Consequence: PGAP2 NM_001346403.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300
• Publications: 1 publications found

Genes affected

PGAP2 (HGNC:17893): (post-GPI attachment to proteins 2) The protein encoded by this gene plays a role in the maturation of glycosylphosphatidylinositol (GPI) anchors on GPI-anchored proteins. Mutations in this gene are associated with an autosomal recessive syndrome characterized by hyperphosphatasia and intellectual disability. [provided by RefSeq, Jul 2017]

PGAP2 Gene-Disease associations (from GenCC):

• hyperphosphatasia with intellectual disability syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hyperphosphatasia-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-3808066-CCGG-C is Benign according to our data. Variant chr11-3808066-CCGG-C is described in ClinVar as Benign. ClinVar VariationId is 1220981.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346403.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAP2	NM_001346403.1		c.-53_-51delCGG		5_prime_UTR	Exon 1 of 8	NP_001333332.1
	PGAP2	NM_001346405.1		c.-53_-51delCGG		5_prime_UTR	Exon 1 of 7	NP_001333334.1	Q9UHJ9-1
	PGAP2	NM_001346404.1		c.-53_-51delCGG		5_prime_UTR	Exon 1 of 7	NP_001333333.1	H0YDQ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGAP2	ENST00000300730.10	TSL:1	c.140-227_140-225delCGG		intron	N/A	ENSP00000300730.6	Q9UHJ9-5
	PGAP2	ENST00000396993.8	TSL:1	c.-325-227_-325-225delCGG		intron	N/A	ENSP00000380190.6	A8MZF5
	PGAP2	ENST00000465237.6	TSL:1	n.76-227_76-225delCGG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13782 AN: 152106 Hom.: 851 Cov.: 28

Gnomad AFR AF: 0.0231

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.118 AC: 149820 AN: 1271234 Hom.: 9555 AF XY: 0.117 AC XY: 71950 AN XY: 616764

African (AFR) AF: 0.0200 AC: 555 AN: 27786

American (AMR) AF: 0.0990 AC: 1982 AN: 20016

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 2354 AN: 18526

East Asian (EAS) AF: 0.000441 AC: 15 AN: 33980

South Asian (SAS) AF: 0.0596 AC: 3684 AN: 61850

European-Finnish (FIN) AF: 0.0926 AC: 2812 AN: 30366

Middle Eastern (MID) AF: 0.149 AC: 529 AN: 3540

European-Non Finnish (NFE) AF: 0.129 AC: 132270 AN: 1022612

Other (OTH) AF: 0.107 AC: 5619 AN: 52558

GnomAD4 genome AF: 0.0905 AC: 13778 AN: 152224 Hom.: 850 Cov.: 28 AF XY: 0.0889 AC XY: 6619 AN XY: 74432

African (AFR) AF: 0.0231 AC: 959 AN: 41550

American (AMR) AF: 0.113 AC: 1731 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.0505 AC: 244 AN: 4830

European-Finnish (FIN) AF: 0.0917 AC: 973 AN: 10612

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8951 AN: 67986

Other (OTH) AF: 0.115 AC: 242 AN: 2110

Alfa AF: 0.105 Hom.: 116

Bravo AF: 0.0901

Asia WGS AF: 0.0260 AC: 90 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.030
Mutation Taster		=299/1	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: rs75108073; hg19: chr11-3829296; COSMIC: COSV53463763; COSMIC: COSV53463763;