chr10-48189312-T-C

Variant names:

• chr10-48189312-T-C
• rs1367024
• NM_001018071.4:c.2166-2020A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Benign. The variant received -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.

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.2166-2020A>G		intron	N/A	NP_001018081.4
	FRMPD2	NM_001318191.1		c.2091-2020A>G		intron	N/A	NP_001305120.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD2	ENST00000374201.8	TSL:1 MANE Select	c.2166-2020A>G		intron	N/A	ENSP00000363317.3
	FRMPD2	ENST00000636244.1	TSL:5	c.2166-2020A>G		intron	N/A	ENSP00000490201.1
	FRMPD2	ENST00000305531.3	TSL:5	c.2091-2020A>G		intron	N/A	ENSP00000307079.3

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

African (AFR) AF: 0.170 AC: 7067 AN: 41456

American (AMR) AF: 0.163 AC: 2497 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 866 AN: 3470

East Asian (EAS) AF: 0.0754 AC: 390 AN: 5172

South Asian (SAS) AF: 0.192 AC: 928 AN: 4824

European-Finnish (FIN) AF: 0.302 AC: 3191 AN: 10580

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17844 AN: 67944

Other (OTH) AF: 0.206 AC: 434 AN: 2108

Alfa AF: 0.227 Hom.: 1903

Bravo AF: 0.208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.82
DANN	Benign	0.46
PhyloP100		-0.070
Mutation Taster		=100/0	polymorphism (auto)

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: rs1367024; hg19: chr10-49397355;