Genetic Variant FRMPD2:p.Gln1118Arg (chr10-48171079-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. Variant has been reported in ClinVar as Uncertain significance (★).

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4 link	c.3353A>G	p.Gln1118Arg	missense_variant	Exon 26 of 29	ENST00000374201.8	NP_001018081.4	Q68DX3-1B4E1N9
FRMPD2	NM_001318191.1 link	c.3278A>G	p.Gln1093Arg	missense_variant	Exon 24 of 27		NP_001305120.1	Q68DX3
FRMPD2	NM_001042512.3 link	c.386A>G	p.Gln129Arg	missense_variant	Exon 3 of 6		NP_001035977.3	Q68DX3-4
FRMPD2	XM_017015744.2 link	c.209A>G	p.Gln70Arg	missense_variant	Exon 3 of 6		XP_016871233.1	Q68DX3-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD2	ENST00000374201.8 link	c.3353A>G	p.Gln1118Arg	missense_variant	Exon 26 of 29	1	NM_001018071.4	ENSP00000363317.3		Q68DX3-1

Frequencies

GnomAD3 genomes

AF:

0.000156

AC:

AN:

147196

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.000139

AC:

AN:

36052

AF XY:

0.000217

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 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

African (AFR)

AF:

0.000586

AC:

AN:

20464

American (AMR)

AF:

0.000118

AC:

AN:

42330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20908

East Asian (EAS)

AF:

0.00

AC:

AN:

35842

South Asian (SAS)

AF:

0.00

AC:

AN:

70252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

425006

Other (OTH)

AF:

0.0000853

AC:

AN:

35160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

African (AFR)

AF:

0.000419

AC:

AN:

40620

American (AMR)

AF:

0.000343

AC:

AN:

14580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3384

East Asian (EAS)

AF:

0.00

AC:

AN:

5068

South Asian (SAS)

AF:

0.00

AC:

AN:

4386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9714

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66414

Other (OTH)

AF:

0.00102

AC:

AN:

1962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

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

Dec 07, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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;.

PhyloP100

5.2

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

Mutation Taster

=85/15

polymorphism

(source)

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

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10-48171079-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over