NM_005374.5:c.151-728G>A

Variant names:

• chr17-43884083-C-T
• rs231518
• NM_005374.5:c.151-728G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 20 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005374.5. 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
	MPP2	NM_005374.5	MANE Select	c.151-728G>A		intron	N/A	NP_005365.4
	MPP2	NM_001278370.2		c.286-728G>A		intron	N/A	NP_001265299.1	A0A0C4DH75
	MPP2	NM_001278372.2		c.222+1G>A		splice_donor intron	N/A	NP_001265301.1	D3DX49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP2	ENST00000269095.9	TSL:1 MANE Select	c.151-728G>A		intron	N/A	ENSP00000269095.4	D3DX48
	MPP2	ENST00000461854.5	TSL:1	c.222+1G>A		splice_donor intron	N/A	ENSP00000428286.1	D3DX49
	MPP2	ENST00000377184.7	TSL:1	c.202-728G>A		intron	N/A	ENSP00000366389.3	A0A0A0MRU0

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17627 AN: 152082 Hom.: 1146 Cov.: 32

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.: 0 AF XY: 0.122 AC XY: 36313 AN XY: 297780

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: 7 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

GnomAD4 genome AF: 0.116 AC: 17628 AN: 152200 Hom.: 1147 Cov.: 32 AF XY: 0.114 AC XY: 8507 AN XY: 74400

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: 5 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: 42 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9236 AN: 67996

Other (OTH) AF: 0.114 AC: 241 AN: 2110

Alfa AF: 0.126 Hom.: 1027

Bravo AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.3
PhyloP100		-0.26

Splicing

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

Other links and lift over

dbSNP: rs231518; hg19: chr17-41961451;