rs1346694

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr10-48180973-T-C
• chr10-48180973-T-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.2620A>G​(p.Ser874Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.46 (10987 hom., cov: 25)
  • Exomes 𝑓: 0.49 (73896 hom.)
  • Failed GnomAD Quality Control
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.039671E-4).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD2	NM_001018071.4	MANE Select	c.2620A>G	p.Ser874Gly	missense	Exon 21 of 29	NP_001018081.4	Q68DX3-1
	FRMPD2	NM_001318191.1		c.2545A>G	p.Ser849Gly	missense	Exon 19 of 27	NP_001305120.1	Q68DX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMPD2	ENST00000374201.8	TSL:1 MANE Select	c.2620A>G	p.Ser874Gly	missense	Exon 21 of 29	ENSP00000363317.3	Q68DX3-1
	FRMPD2	ENST00000636244.1	TSL:5	c.2620A>G	p.Ser874Gly	missense	Exon 21 of 30	ENSP00000490201.1	A0A1B0GUQ4
	FRMPD2	ENST00000305531.3	TSL:5	c.2545A>G	p.Ser849Gly	missense	Exon 19 of 27	ENSP00000307079.3	Q68DX3-2

Frequencies

GnomAD3 genomes AF: 0.461 AC: 63514 AN: 137824 Hom.: 10984 Cov.: 25

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.459

GnomAD2 exomes AF: 0.553 AC: 42881 AN: 77600 AF XY: 0.552

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.459

Gnomad ASJ exome AF: 0.611

Gnomad EAS exome AF: 0.525

Gnomad FIN exome AF: 0.664

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.546

GnomAD4 exome AF: 0.485 AC: 364555 AN: 751400 Hom.: 73896 Cov.: 10 AF XY: 0.488 AC XY: 194050 AN XY: 398042

African (AFR) AF: 0.374 AC: 7794 AN: 20818

American (AMR) AF: 0.417 AC: 16922 AN: 40602

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 11423 AN: 20572

East Asian (EAS) AF: 0.443 AC: 15887 AN: 35840

South Asian (SAS) AF: 0.400 AC: 27929 AN: 69792

European-Finnish (FIN) AF: 0.608 AC: 30057 AN: 49422

Middle Eastern (MID) AF: 0.496 AC: 1337 AN: 2698

European-Non Finnish (NFE) AF: 0.496 AC: 235761 AN: 475626

Other (OTH) AF: 0.484 AC: 17445 AN: 36030

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.461 AC: 63545 AN: 137938 Hom.: 10987 Cov.: 25 AF XY: 0.462 AC XY: 31019 AN XY: 67114

African (AFR) AF: 0.375 AC: 14377 AN: 38372

American (AMR) AF: 0.411 AC: 5776 AN: 14054

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1682 AN: 3126

East Asian (EAS) AF: 0.465 AC: 2241 AN: 4824

South Asian (SAS) AF: 0.356 AC: 1545 AN: 4340

European-Finnish (FIN) AF: 0.566 AC: 5179 AN: 9158

Middle Eastern (MID) AF: 0.468 AC: 117 AN: 250

European-Non Finnish (NFE) AF: 0.512 AC: 31317 AN: 61122

Other (OTH) AF: 0.454 AC: 858 AN: 1890

Alfa AF: 0.543 Hom.: 2513

ExAC AF: 0.512 AC: 3919

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.00020	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.79
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.055
Sift	Benign	0.14	T
Sift4G	Uncertain	0.017	D
Polyphen		0.0020	B
Vest4		0.036
MPC		0.029
ClinPred		0.0075	T
GERP RS		1.3
Varity_R		0.083
gMVP		0.21
Mutation Taster		=99/1	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: rs1346694; hg19: chr10-49389016; COSMIC: COSV59714717; COSMIC: COSV59714717;