chr11-3811371-A-G

Position:

• chr11-3811371-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Moderate BP6_Moderate

The NM_014489.4(PGAP2):​c.112A>G​(p.Ile38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGAP2 NM_014489.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.24

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]

LOC124902618 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a chain Post-GPI attachment to proteins factor 2 (size 253) in uniprot entity PGAP2_HUMAN there are 26 pathogenic changes around while only 5 benign (84%) in NM_014489.4
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10784286).
• BP6: Variant 11-3811371-A-G is Benign according to our data. Variant chr11-3811371-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2429794.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGAP2	NM_014489.4	c.112A>G	p.Ile38Val	missense_variant	2/7	ENST00000278243.9
LOC124902618	XR_007062559.1	n.346T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGAP2	ENST00000278243.9	c.112A>G	p.Ile38Val	missense_variant	2/7	1	NM_014489.4	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism spectrum disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine

Apr 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.89
DEOGEN2	Benign	0.19	.;.;.;.;.;.;.;T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.85	D;D;D;D;.;D;T;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.10	.;.;.;.;N;N;N;N;.
MutationTaster	Benign	0.97	D;D;D;D;D;D;D;D;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.060	N;N;.;.;.;N;N;N;N
REVEL	Benign	0.077
Sift	Benign	0.75	T;T;.;.;.;T;T;T;T
Sift4G	Benign	0.70	T;T;T;T;T;T;T;T;T
Polyphen		0.070	B;.;.;.;.;.;.;B;.
Vest4		0.18
MutPred		0.51		Loss of catalytic residue at L100 (P = 0.0801);Loss of catalytic residue at L100 (P = 0.0801);.;.;.;.;.;.;.;
MVP		0.38
MPC		0.30
ClinPred		0.25	T
GERP RS		2.1
Varity_R		0.022
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-3832601;