10-48178141-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.76

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]

ACMG classification

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 GnomAdExome at 3 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000736 AC: 112 AN: 152162 Hom.: 1 Cov.: 30

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.: 3 AF XY: 0.00238 AC XY: 177 AN XY: 74370

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.: 25 Cov.: 21 AF XY: 0.00147 AC XY: 1015 AN XY: 688202

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.: 1 Cov.: 30 AF XY: 0.000873 AC XY: 65 AN XY: 74454

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.: 1

Bravo AF: 0.000499

ExAC AF: 0.000863 AC: 92

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.039	T;T;.
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.75	T;T;T
MetaRNN	Benign	0.0093	T;T;T
MetaSVM	Benign	-0.84	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.35	T
Polyphen		0.33, 0.98	.;B;D
Vest4		0.16, 0.19
MVP		0.66
MPC		3.1
ClinPred		0.098	T
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

Other links and lift over

dbSNP: rs200783524; hg19: chr10-49386184;