Genetic Variant NM_005374.5:c.151-728G>A (chr17-43884083-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005374.5(MPP2):c.151-728G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 702,314 control chromosomes in the GnomAD database, including 5,916 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 0.12 ( 1147 hom., cov: 32)

Exomes 𝑓: 0.12 ( 4769 hom. )

Consequence

MPP2
NM_005374.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.263

Publications

20 publications found

Variant links:

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]

MPP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP2	NM_005374.5 link	c.151-728G>A		intron_variant	Intron 3 of 12	ENST00000269095.9	NP_005365.4	Q14168D3DX48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP2	ENST00000269095.9 link	c.151-728G>A		intron_variant	Intron 3 of 12	1	NM_005374.5	ENSP00000269095.4		D3DX48
MPP2	ENST00000461854.5 link	c.222+1G>A		splice_donor_variant, intron_variant	Intron 4 of 13	1		ENSP00000428286.1		D3DX49

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17627

AN:

152082

Hom.:

1146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0989

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.0857

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.000960

Gnomad SAS

AF:

0.0910

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.115

GnomAD4 exome

AF:

0.122

AC:

66965

AN:

550114

Hom.:

4769

Cov.:

AF XY:

0.122

AC XY:

36313

AN XY:

297780

show subpopulations

African (AFR)

AF:

0.104

AC:

1636

AN:

15802

American (AMR)

AF:

0.0669

AC:

2317

AN:

34652

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

3540

AN:

20012

East Asian (EAS)

AF:

0.000218

AC:

AN:

32086

South Asian (SAS)

AF:

0.0969

AC:

6065

AN:

62608

European-Finnish (FIN)

AF:

0.156

AC:

5245

AN:

33592

Middle Eastern (MID)

AF:

0.158

AC:

642

AN:

4070

European-Non Finnish (NFE)

AF:

0.138

AC:

43837

AN:

316702

Other (OTH)

AF:

0.120

AC:

3676

AN:

30590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

2719

5438

8157

10876

13595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.116

AC:

17628

AN:

152200

Hom.:

1147

Cov.:

AF XY:

0.114

AC XY:

8507

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0988

AC:

4104

AN:

41520

American (AMR)

AF:

0.0856

AC:

1309

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

606

AN:

3472

East Asian (EAS)

AF:

0.000962

AC:

AN:

5196

South Asian (SAS)

AF:

0.0907

AC:

437

AN:

4818

European-Finnish (FIN)

AF:

0.145

AC:

1536

AN:

10588

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9236

AN:

67996

Other (OTH)

AF:

0.114

AC:

241

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

793

1587

2380

3174

3967

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.126

Hom.:

1027

Bravo

AF:

0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.3

(source)

PhyloP100

-0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over