17-43882352-G-T

Variant names:

• chr17-43882352-G-T
• rs544561497
• NM_005374.5:c.613C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005374.5(MPP2):​c.613C>A​(p.Arg205Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MPP2 NM_005374.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

Genes affected

MPP2 (HGNC:7220): (MAGUK p55 scaffold protein 2) Palmitoylated membrane protein 2 is a member of a family of membrane-associated proteins termed MAGUKs (membrane-associated guanylate kinase homologs). MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intracellular junctions. Palmitoylated membrane protein 2 contains a conserved sequence, called the SH3 (src homology 3) motif, found in several other proteins that associate with the cytoskeleton and are suspected to play important roles in signal transduction. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30063742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP2	NM_005374.5	c.613C>A	p.Arg205Ser	missense_variant	Exon 6 of 13	ENST00000269095.9	NP_005365.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP2	ENST00000269095.9	c.613C>A	p.Arg205Ser	missense_variant	Exon 6 of 13	1	NM_005374.5	ENSP00000269095.4
MPP2	ENST00000461854.5	c.685C>A	p.Arg229Ser	missense_variant	Exon 7 of 14	1		ENSP00000428286.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249734 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135288

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460066 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726516

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	.;.;.;.;T;.;.;.;.;T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.89	D;.;.;D;D;D;D;D;.;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.30	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.8	D;D;D;.;.;.;D;N;D;D;D
REVEL	Benign	0.16
Sift	Benign	0.39	T;T;T;.;.;.;T;T;T;T;D
Sift4G	Benign	0.18	T;T;T;T;T;T;T;T;T;T;.
Vest4		0.45
MutPred		0.53		.;.;.;.;.;.;Gain of disorder (P = 0.0576);.;.;.;.;
MVP		0.76
MPC		1.0
ClinPred		0.27	T
GERP RS		3.6
gMVP		0.51

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: rs544561497; hg19: chr17-41959720;