10-48163621-G-A

Variant names:

• chr10-48163621-G-A
• rs201205821
• NM_001018071.4:c.3588C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001018071.4(FRMPD2):​c.3588C>T​(p.Asp1196Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,312,982 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (1 hom., cov: 28)
  • Exomes 𝑓: 0.00026 (2 hom.)
• Consequence: FRMPD2 NM_001018071.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.135

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-48163621-G-A is Benign according to our data. Variant chr10-48163621-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.135 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRMPD2	NM_001018071.4	c.3588C>T	p.Asp1196Asp	synonymous_variant	Exon 28 of 29	ENST00000374201.8	NP_001018081.4
FRMPD2	NM_001318191.1	c.3513C>T	p.Asp1171Asp	synonymous_variant	Exon 26 of 27		NP_001305120.1
FRMPD2	NM_001042512.3	c.621C>T	p.Asp207Asp	synonymous_variant	Exon 5 of 6		NP_001035977.3
FRMPD2	XM_017015744.2	c.444C>T	p.Asp148Asp	synonymous_variant	Exon 5 of 6		XP_016871233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRMPD2	ENST00000374201.8	c.3588C>T	p.Asp1196Asp	synonymous_variant	Exon 28 of 29	1	NM_001018071.4	ENSP00000363317.3

Frequencies

GnomAD3 genomes AF: 0.000193 AC: 29 AN: 150240 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.000124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000355

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000122 AC: 27 AN: 220882 AF XY: 0.0000835

Gnomad AFR exome AF: 0.0000723

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000260

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000265 AC: 308 AN: 1162742 Hom.: 2 Cov.: 17 AF XY: 0.000267 AC XY: 158 AN XY: 592670

African (AFR) AF: 0.000113 AC: 3 AN: 26486

American (AMR) AF: 0.00 AC: 0 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24172

East Asian (EAS) AF: 0.00 AC: 0 AN: 38206

South Asian (SAS) AF: 0.00 AC: 0 AN: 80210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3546

European-Non Finnish (NFE) AF: 0.000332 AC: 280 AN: 842350

Other (OTH) AF: 0.000499 AC: 25 AN: 50146

GnomAD4 genome AF: 0.000193 AC: 29 AN: 150240 Hom.: 1 Cov.: 28 AF XY: 0.000164 AC XY: 12 AN XY: 73318

African (AFR) AF: 0.000124 AC: 5 AN: 40280

American (AMR) AF: 0.00 AC: 0 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000355 AC: 24 AN: 67696

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.000240 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FRMPD2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.84
DANN	Benign	0.21
PhyloP100		-0.14

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

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Other links and lift over

dbSNP: rs201205821; hg19: chr10-49371664;