rs376780885

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001018071.4(FRMPD2):c.3200C>T(p.Ser1067Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000078 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000039 ( 13 hom. )

Failed GnomAD Quality Control

Consequence

FRMPD2
NM_001018071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0160

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4 link	c.3200C>T	p.Ser1067Leu	missense_variant	Exon 25 of 29	ENST00000374201.8	NP_001018081.4	Q68DX3-1B4E1N9
FRMPD2	NM_001318191.1 link	c.3125C>T	p.Ser1042Leu	missense_variant	Exon 23 of 27		NP_001305120.1	Q68DX3
FRMPD2	NM_001042512.3 link	c.233C>T	p.Ser78Leu	missense_variant	Exon 2 of 6		NP_001035977.3	Q68DX3-4
FRMPD2	XM_017015744.2 link	c.56C>T	p.Ser19Leu	missense_variant	Exon 2 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.3200C>T	p.Ser1067Leu	missense_variant	Exon 25 of 29	1	NM_001018071.4	ENSP00000363317.3		Q68DX3-1

Frequencies

GnomAD3 genomes

AF:

0.00000785

AC:

AN:

127414

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000178

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000682

AC:

AN:

219952

AF XY:

0.0000673

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000640

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000593

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000395

AC:

AN:

1089760

Hom.:

Cov.:

AF XY:

0.0000401

AC XY:

AN XY:

549232

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30920

American (AMR)

AF:

0.0000493

AC:

AN:

40552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20260

East Asian (EAS)

AF:

0.0000269

AC:

AN:

37106

South Asian (SAS)

AF:

0.0000512

AC:

AN:

78052

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3252

European-Non Finnish (NFE)

AF:

0.0000396

AC:

AN:

783376

Other (OTH)

AF:

0.0000844

AC:

AN:

47398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000785

AC:

AN:

127414

Hom.:

Cov.:

AF XY:

0.0000163

AC XY:

AN XY:

61312

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37446

American (AMR)

AF:

0.00

AC:

AN:

12986

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2834

East Asian (EAS)

AF:

0.00

AC:

AN:

4284

South Asian (SAS)

AF:

0.00

AC:

AN:

3926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.0000178

AC:

AN:

56230

Other (OTH)

AF:

0.00

AC:

AN:

1636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.825

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000921

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 19, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3200C>T (p.S1067L) alteration is located in exon 25 (coding exon 25) of the FRMPD2 gene. This alteration results from a C to T substitution at nucleotide position 3200, causing the serine (S) at amino acid position 1067 to be replaced by a leucine (L). 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

Benign

0.077

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.018

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.53

T;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.

PhyloP100

-0.016

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.3

.;N;N

REVEL

Benign

0.022

Sift

Benign

0.23

.;T;T

Sift4G

Benign

0.18

.;T;T

Polyphen

0.045, 0.024

.;B;B

Vest4

0.056, 0.042

MVP

0.12

MPC

1.5

ClinPred

0.034

GERP RS

-1.1

Varity_R

0.036

gMVP

0.12

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.30

Position offset: 26

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs376780885

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over