rs169439

Positions:

• chr10-48242632-C-A
• chr10-48242632-C-G

Variant summary

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

The NM_001018071.4(FRMPD2):​c.376-280G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,262 control chromosomes in the GnomAD database, including 54,747 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 0.82 (54747 hom., cov: 34)
• Consequence: FRMPD2 NM_001018071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

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 (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRMPD2	NM_001018071.4	c.376-280G>T		intron_variant		ENST00000374201.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRMPD2	ENST00000374201.8	c.376-280G>T		intron_variant		1	NM_001018071.4	P2

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125403 AN: 152144 Hom.: 54719 Cov.: 34

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.863

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

GnomAD4 genome AF: 0.824 AC: 125479 AN: 152262 Hom.: 54747 Cov.: 34 AF XY: 0.831 AC XY: 61863 AN XY: 74460

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.891

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.952

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.865

Alfa AF: 0.927 Hom.: 88169

Bravo AF: 0.805

Asia WGS AF: 0.958 AC: 3331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.39
DANN	Benign	0.36

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: rs169439; hg19: chr10-49450675;