1-176597214-C-T

Position:

• chr1-176597214-C-T

Variant summary

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

The NM_020318.3(PAPPA2):​c.1991+1619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,114 control chromosomes in the GnomAD database, including 2,211 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 (2211 hom., cov: 32)
• Consequence: PAPPA2 NM_020318.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAPPA2	NM_020318.3	c.1991+1619C>T		intron_variant		ENST00000367662.5	NP_064714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPPA2	ENST00000367662.5	c.1991+1619C>T		intron_variant		1	NM_020318.3	ENSP00000356634.3
PAPPA2	ENST00000367661.7	c.1991+1619C>T		intron_variant		1		ENSP00000356633.3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25260 AN: 151996 Hom.: 2212 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.166 AC: 25255 AN: 152114 Hom.: 2211 Cov.: 32 AF XY: 0.165 AC XY: 12278 AN XY: 74358

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.175

Alfa AF: 0.173 Hom.: 1226

Bravo AF: 0.162

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs10489478; hg19: chr1-176566350;