Variant 10-48178141-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001018071.4(FRMPD2):c.2801C>A(p.Ser934Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,525,474 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0011 ( 25 hom. )

Consequence

FRMPD2
NM_001018071.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.76

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009323031).

BP6

Variant 10-48178141-G-T is Benign according to our data. Variant chr10-48178141-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640440.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FRMPD2	NM_001018071.4 linkuse as main transcript	c.2801C>A	p.Ser934Tyr	missense_variant	22/29	ENST00000374201.8
FRMPD2	NM_001318191.1 linkuse as main transcript	c.2726C>A	p.Ser909Tyr	missense_variant	20/27
FRMPD2	XM_047424652.1 linkuse as main transcript	c.2798C>A	p.Ser933Tyr	missense_variant	22/22
FRMPD2	XM_047424653.1 linkuse as main transcript	c.2708C>A	p.Ser903Tyr	missense_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMPD2	ENST00000374201.8 linkuse as main transcript	c.2801C>A	p.Ser934Tyr	missense_variant	22/29	1	NM_001018071.4	P2	Q68DX3-1

Frequencies

GnomAD3 genomes

AF:

0.000736

AC:

112

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00912

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00175

AC:

247

AN:

141512

Hom.:

AF XY:

0.00238

AC XY:

177

AN XY:

74370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000714

Gnomad ASJ exome

AF:

0.00168

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00854

Gnomad FIN exome

AF:

0.000207

Gnomad NFE exome

AF:

0.000796

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00112

AC:

1536

AN:

1373194

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1015

AN XY:

688202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.000810

Gnomad4 ASJ exome

AF:

0.00219

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000456

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152280

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00934

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000754

Hom.:

Bravo

AF:

0.000499

ExAC

AF:

0.000863

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

FRMPD2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

T;T;.

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

T;T;T

MetaRNN

Benign

0.0093

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.0

.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.8

.;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.0020

.;D;D

Sift4G

Uncertain

0.011

.;D;D

Polyphen

0.33, 0.98

.;B;D

Vest4

0.16, 0.19

MVP

0.66

MPC

3.1

ClinPred

0.098

GERP RS

3.8

Varity_R

0.19

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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