dbSNP rs782232511: FRMPD2:p.Cys1009Phe (chr10-48174919-C-A) – 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.3026G>T(p.Cys1009Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1009Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 14)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FRMPD2
NM_001018071.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.64

Publications

1 publications found

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:

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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=0.20478263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4 link	c.3026G>T	p.Cys1009Phe	missense_variant	Exon 24 of 29	ENST00000374201.8	NP_001018081.4	Q68DX3-1B4E1N9
FRMPD2	NM_001318191.1 link	c.2951G>T	p.Cys984Phe	missense_variant	Exon 22 of 27		NP_001305120.1	Q68DX3
FRMPD2	NM_001042512.3 link	c.59G>T	p.Cys20Phe	missense_variant	Exon 1 of 6		NP_001035977.3	Q68DX3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD2	ENST00000374201.8 link	c.3026G>T	p.Cys1009Phe	missense_variant	Exon 24 of 29	1	NM_001018071.4	ENSP00000363317.3		Q68DX3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

553426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

295994

African (AFR)

AF:

0.00

AC:

AN:

17240

American (AMR)

AF:

0.00

AC:

AN:

29886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18988

East Asian (EAS)

AF:

0.00

AC:

AN:

32520

South Asian (SAS)

AF:

0.00

AC:

AN:

58476

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

315796

Other (OTH)

AF:

0.00

AC:

AN:

29598

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.085

T;T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.3

.;N;.

PhyloP100

2.6

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.0

.;D;D

REVEL

Benign

0.12

Sift

Benign

0.032

.;D;D

Sift4G

Benign

0.14

.;T;T

Polyphen

1.0, 1.0

.;D;D

Vest4

0.32, 0.30

MutPred

0.51

Loss of ubiquitination at K1014 (P = 0.1154);Loss of ubiquitination at K1014 (P = 0.1154);.;

MVP

0.25

MPC

3.3

ClinPred

0.92

GERP RS

2.0

Varity_R

0.36

gMVP

0.17

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over