rs764274557

Variant names:

• chr1-176556602-C-A
• NM_020318.3:c.280C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-176556602-C-A
• chr1-176556602-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020318.3(PAPPA2):​c.280C>A​(p.Arg94Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAPPA2 NM_020318.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324

Genes affected

PAPPA2 (HGNC:14615): (pappalysin 2) This gene encodes a member of the pappalysin family of metzincin metalloproteinases. The encoded protein cleaves insulin-like growth factor-binding protein 5 and is thought to be a local regulator of insulin-like growth factor (IGF) bioavailability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05537331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPPA2	NM_020318.3	c.280C>A	p.Arg94Ser	missense_variant	Exon 2 of 23	ENST00000367662.5	NP_064714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPPA2	ENST00000367662.5	c.280C>A	p.Arg94Ser	missense_variant	Exon 2 of 23	1	NM_020318.3	ENSP00000356634.3
PAPPA2	ENST00000367661.7	c.280C>A	p.Arg94Ser	missense_variant	Exon 2 of 5	1		ENSP00000356633.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.2
DANN	Benign	0.64
DEOGEN2	Benign	0.056	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-0.35	N;N
REVEL	Benign	0.038
Sift	Benign	0.59	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.013	.;B
Vest4		0.10
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.24
MPC		0.20
ClinPred		0.030	T
GERP RS		-1.0
Varity_R		0.085
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-176525738;