rs231480

Variant names:

• chr17-43906130-G-A
• rs231480
• NM_005374.5:c.-34+1344C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-43906130-G-A
• chr17-43906130-G-C

Variant summary

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

The NM_005374.5(MPP2):​c.-34+1344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 975,616 control chromosomes in the GnomAD database, including 68,494 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 0.43 (14826 hom., cov: 32)
  • Exomes 𝑓: 0.36 (53668 hom.)
• Consequence: MPP2 NM_005374.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP2	NM_005374.5	MANE Select	c.-34+1344C>T		intron	N/A	NP_005365.4
	MPP2	NM_001278381.2		c.-84C>T		5_prime_UTR	Exon 2 of 14	NP_001265310.1
	MPP2	NM_001278370.2		c.103-1637C>T		intron	N/A	NP_001265299.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP2	ENST00000269095.9	TSL:1 MANE Select	c.-34+1344C>T		intron	N/A	ENSP00000269095.4
	MPP2	ENST00000461854.5	TSL:1	c.-34+1344C>T		intron	N/A	ENSP00000428286.1
	MPP2	ENST00000523220.5	TSL:1	c.-3+1344C>T		intron	N/A	ENSP00000428468.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65399 AN: 151638 Hom.: 14802 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.355 AC: 292627 AN: 823860 Hom.: 53668 Cov.: 29 AF XY: 0.356 AC XY: 135307 AN XY: 380562

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.505 AC: 7868 AN: 15588

American (AMR) AF: 0.626 AC: 605 AN: 966

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1834 AN: 5110

East Asian (EAS) AF: 0.660 AC: 2375 AN: 3600

South Asian (SAS) AF: 0.549 AC: 8916 AN: 16250

European-Finnish (FIN) AF: 0.327 AC: 93 AN: 284

Middle Eastern (MID) AF: 0.328 AC: 526 AN: 1604

European-Non Finnish (NFE) AF: 0.345 AC: 259893 AN: 753496

Other (OTH) AF: 0.390 AC: 10517 AN: 26962

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.431 AC: 65460 AN: 151756 Hom.: 14826 Cov.: 32 AF XY: 0.439 AC XY: 32526 AN XY: 74150

African (AFR) AF: 0.499 AC: 20636 AN: 41380

American (AMR) AF: 0.537 AC: 8204 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1321 AN: 3466

East Asian (EAS) AF: 0.668 AC: 3420 AN: 5118

South Asian (SAS) AF: 0.575 AC: 2768 AN: 4814

European-Finnish (FIN) AF: 0.371 AC: 3913 AN: 10542

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.353 AC: 23971 AN: 67872

Other (OTH) AF: 0.407 AC: 855 AN: 2102

Alfa AF: 0.405 Hom.: 1693

Bravo AF: 0.445

Asia WGS AF: 0.629 AC: 2190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.25
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs231480; hg19: chr17-41983498;