chr10-48180973-T-G

Variant names:

• chr10-48180973-T-G
• rs1346694
• NM_001018071.4:c.2620A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001018071.4(FRMPD2):​c.2620A>C​(p.Ser874Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 25)
• Consequence: FRMPD2 NM_001018071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791
• Publications: 10 publications found

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

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.111320496).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018071.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD2	NM_001018071.4	MANE Select	c.2620A>C	p.Ser874Arg	missense	Exon 21 of 29	NP_001018081.4
	FRMPD2	NM_001318191.1		c.2545A>C	p.Ser849Arg	missense	Exon 19 of 27	NP_001305120.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD2	ENST00000374201.8	TSL:1 MANE Select	c.2620A>C	p.Ser874Arg	missense	Exon 21 of 29	ENSP00000363317.3
	FRMPD2	ENST00000636244.1	TSL:5	c.2620A>C	p.Ser874Arg	missense	Exon 21 of 30	ENSP00000490201.1
	FRMPD2	ENST00000305531.3	TSL:5	c.2545A>C	p.Ser849Arg	missense	Exon 19 of 27	ENSP00000307079.3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 10

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.79
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.10
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.87	P
Vest4		0.092
MutPred		0.20		Loss of glycosylation at S874 (P = 0.0182)
MVP		0.48
MPC		0.033
ClinPred		0.23	T
GERP RS		1.3
Varity_R		0.15
gMVP		0.30
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1346694; hg19: chr10-49389016;