Variant 10-48171079-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001018071.4(FRMPD2):c.3353A>G(p.Gln1118Arg) variant causes a missense change. 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 0.00016 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FRMPD2
NM_001018071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

Variant links:

Genes affected

FRMPD2 (HGNC:28572): (FERM and PDZ domain containing 2) This gene encodes a peripheral membrane protein and is located in a region of chromosome 10q that contains a segmental duplication. This copy of the gene is full-length and is in the telomeric duplicated region. Two other more centromerically proximal copies of the gene are partial and may represent pseudogenes. This full-length gene appears to function in the establishment and maintenance of cell polarization. The protein is recruited to cell-cell junctions in an E-cadherin-dependent manner, and is selectively localized at the basolateral membrane in polarized epithelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2009]

FRMPD2 links:

FRMPD2 (HGNC:):

FRMPD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16823322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRMPD2	NM_001018071.4 linkuse as main transcript	c.3353A>G	p.Gln1118Arg	missense_variant	26/29	ENST00000374201.8	NP_001018081.4	Q68DX3-1B4E1N9
FRMPD2	NM_001318191.1 linkuse as main transcript	c.3278A>G	p.Gln1093Arg	missense_variant	24/27		NP_001305120.1	Q68DX3
FRMPD2	NM_001042512.3 linkuse as main transcript	c.386A>G	p.Gln129Arg	missense_variant	3/6		NP_001035977.3	Q68DX3-4
FRMPD2	XM_017015744.2 linkuse as main transcript	c.209A>G	p.Gln70Arg	missense_variant	3/6		XP_016871233.1	Q68DX3-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRMPD2	ENST00000374201.8 linkuse as main transcript	c.3353A>G	p.Gln1118Arg	missense_variant	26/29	1	NM_001018071.4	ENSP00000363317.3		Q68DX3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147196

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000395

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000343

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00103

GnomAD3 exomes

AF:

0.000139

AC:

AN:

36052

Hom.:

AF XY:

0.000217

AC XY:

AN XY:

18442

show subpopulations

Gnomad AFR exome

AF:

0.000858

Gnomad AMR exome

AF:

0.000142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000284

AC:

AN:

704700

Hom.:

Cov.:

AF XY:

0.0000187

AC XY:

AN XY:

375108

show subpopulations

Gnomad4 AFR exome

AF:

0.000586

Gnomad4 AMR exome

AF:

0.000118

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:

0.0000853

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000163

AC:

AN:

147314

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

AN XY:

71430

show subpopulations

Gnomad4 AFR

AF:

0.000419

Gnomad4 AMR

AF:

0.000343

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00102

Bravo

AF:

0.000212

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2024

The c.3353A>G (p.Q1118R) alteration is located in exon 26 (coding exon 26) of the FRMPD2 gene. This alteration results from a A to G substitution at nucleotide position 3353, causing the glutamine (Q) at amino acid position 1118 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

.;M;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.3

.;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0060

.;D;D

Sift4G

Uncertain

0.016

.;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.69, 0.59

MVP

0.45

MPC

3.2

ClinPred

0.23

GERP RS

3.3

Varity_R

0.29

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over