10-48178108-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001018071.4(FRMPD2):c.2834C>T(p.Ala945Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,596,226 control chromosomes in the GnomAD database, including 360 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (183 hom., cov: 30)
  • Exomes 𝑓: 0.0027 (177 hom.)
• Consequence: FRMPD2 NM_001018071.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.95

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002079606).
• BP6: Variant 10-48178108-G-A is Benign according to our data. Variant chr10-48178108-G-A is described in ClinVar as [Benign]. Clinvar id is 790083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMPD2	NM_001018071.4	c.2834C>T	p.Ala945Val	missense_variant	22/29	ENST00000374201.8
FRMPD2	NM_001318191.1	c.2759C>T	p.Ala920Val	missense_variant	20/27
FRMPD2	XM_047424652.1	c.2831C>T	p.Ala944Val	missense_variant	22/22
FRMPD2	XM_047424653.1	c.2741C>T	p.Ala914Val	missense_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMPD2	ENST00000374201.8	c.2834C>T	p.Ala945Val	missense_variant	22/29	1	NM_001018071.4	P2

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4074 AN: 152108 Hom.: 181 Cov.: 30

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00675 AC: 1548 AN: 229352 Hom.: 56 AF XY: 0.00495 AC XY: 611 AN XY: 123558

Gnomad AFR exome AF: 0.0966

Gnomad AMR exome AF: 0.00523

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000205

Gnomad OTH exome AF: 0.00496

GnomAD4 exome AF: 0.00265 AC: 3833 AN: 1444000 Hom.: 177 Cov.: 25 AF XY: 0.00220 AC XY: 1583 AN XY: 719602

Gnomad4 AFR exome AF: 0.0935

Gnomad4 AMR exome AF: 0.00557

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000187

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000127

Gnomad4 OTH exome AF: 0.00558

GnomAD4 genome AF: 0.0269 AC: 4090 AN: 152226 Hom.: 183 Cov.: 30 AF XY: 0.0256 AC XY: 1905 AN XY: 74428

Gnomad4 AFR AF: 0.0926

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0110 Hom.: 17

Bravo AF: 0.0303

ESP6500AA AF: 0.0785 AC: 336

ESP6500EA AF: 0.000236 AC: 2

ExAC AF: 0.00755 AC: 909

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	13
Dann	Uncertain	0.98
DEOGEN2	Benign	0.027	T;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.67	T;T;T
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
Polyphen		0.0030, 0.0040	.;B;B
Vest4		0.085, 0.090
MVP		0.11
MPC		1.7
ClinPred		0.0084	T
GERP RS		3.3
Varity_R		0.062
gMVP		0.076

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs150581636; hg19: chr10-49386151;