1-176680045-T-C

Position:

• chr1-176680045-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020318.3(PAPPA2):​c.2137+8930T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,154 control chromosomes in the GnomAD database, including 2,483 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 0.17 (2483 hom., cov: 32)
• Consequence: PAPPA2 NM_020318.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPPA2	NM_020318.3	c.2137+8930T>C		intron_variant		ENST00000367662.5	NP_064714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPPA2	ENST00000367662.5	c.2137+8930T>C		intron_variant		1	NM_020318.3	ENSP00000356634	P1
PAPPA2	ENST00000367661.7	c.2137+8930T>C		intron_variant		1		ENSP00000356633

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26584 AN: 152036 Hom.: 2482 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26587 AN: 152154 Hom.: 2483 Cov.: 32 AF XY: 0.173 AC XY: 12856 AN XY: 74370

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.181

Alfa AF: 0.178 Hom.: 2551

Bravo AF: 0.172

Asia WGS AF: 0.0930 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10454444; hg19: chr1-176649181;