chr10-48189312-T-C

Position:

• chr10-48189312-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001018071.4(FRMPD2):​c.2166-2020A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,052 control chromosomes in the GnomAD database, including 4,004 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4004 hom., cov: 32)
• Consequence: FRMPD2 NM_001018071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMPD2	NM_001018071.4	c.2166-2020A>G		intron_variant		ENST00000374201.8
FRMPD2	NM_001318191.1	c.2091-2020A>G		intron_variant
FRMPD2	XM_047424652.1	c.2163-2020A>G		intron_variant
FRMPD2	XM_047424653.1	c.2073-2020A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMPD2	ENST00000374201.8	c.2166-2020A>G		intron_variant		1	NM_001018071.4	P2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33562 AN: 151936 Hom.: 4002 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.0760

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33581 AN: 152052 Hom.: 4004 Cov.: 32 AF XY: 0.219 AC XY: 16246 AN XY: 74324

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.0754

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.206

Alfa AF: 0.197 Hom.: 854

Bravo AF: 0.208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.82
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs1367024; hg19: chr10-49397355;