rs2293797

Variant names:

• chr14-73258951-C-A
• rs2293797
• NM_001365906.3:c.1628-28C>A

Variant summary

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

The NM_001365906.3(PAPLN):​c.1628-28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,586,834 control chromosomes in the GnomAD database, including 10,914 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 (1197 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9717 hom.)
• Consequence: PAPLN NM_001365906.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• Publications: 8 publications found

Genes affected

PAPLN (HGNC:19262): (papilin, proteoglycan like sulfated glycoprotein) Predicted to enable metalloendopeptidase activity. Predicted to be involved in extracellular matrix organization. Predicted to be located in basement membrane. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPLN	NM_001365906.3	c.1628-28C>A		intron_variant	Intron 14 of 26	ENST00000644200.2	NP_001352835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPLN	ENST00000644200.2	c.1628-28C>A		intron_variant	Intron 14 of 26		NM_001365906.3	ENSP00000495882.2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17617 AN: 152046 Hom.: 1191 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.129 AC: 28727 AN: 223062 AF XY: 0.125

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.0508

Gnomad EAS exome AF: 0.0528

Gnomad FIN exome AF: 0.0864

Gnomad NFE exome AF: 0.0905

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.107 AC: 154174 AN: 1434670 Hom.: 9717 Cov.: 31 AF XY: 0.109 AC XY: 77570 AN XY: 712034

African (AFR) AF: 0.144 AC: 4709 AN: 32798

American (AMR) AF: 0.265 AC: 10989 AN: 41422

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 1244 AN: 24646

East Asian (EAS) AF: 0.0634 AC: 2458 AN: 38774

South Asian (SAS) AF: 0.197 AC: 16199 AN: 82100

European-Finnish (FIN) AF: 0.0836 AC: 4338 AN: 51920

Middle Eastern (MID) AF: 0.0591 AC: 335 AN: 5672

European-Non Finnish (NFE) AF: 0.0982 AC: 107780 AN: 1098042

Other (OTH) AF: 0.103 AC: 6122 AN: 59296

GnomAD4 genome AF: 0.116 AC: 17640 AN: 152164 Hom.: 1197 Cov.: 32 AF XY: 0.117 AC XY: 8677 AN XY: 74386

African (AFR) AF: 0.148 AC: 6147 AN: 41494

American (AMR) AF: 0.173 AC: 2638 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0551 AC: 191 AN: 3468

East Asian (EAS) AF: 0.0688 AC: 356 AN: 5172

South Asian (SAS) AF: 0.204 AC: 983 AN: 4818

European-Finnish (FIN) AF: 0.0814 AC: 863 AN: 10600

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0901 AC: 6130 AN: 68012

Other (OTH) AF: 0.105 AC: 221 AN: 2114

Alfa AF: 0.0994 Hom.: 1582

Bravo AF: 0.125

Asia WGS AF: 0.156 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.29
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2293797; hg19: chr14-73725659; COSMIC: COSV104370686; COSMIC: COSV104370686;