rs2307220

Positions:

• chr12-79592094-A-C
• chr12-79592094-A-G
• chr12-79592094-A-T

Variant summary

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

The NM_002583.4(PAWR):​c.*513T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,506 control chromosomes in the GnomAD database, including 15,397 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 0.35 (15396 hom., cov: 32)
  • Exomes 𝑓: 0.090 (1 hom.)
• Consequence: PAWR NM_002583.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235

Genes affected

PAWR (HGNC:8614): (pro-apoptotic WT1 regulator) This gene encodes a tumor suppressor protein that selectively induces apoptosis in cancer cells through intracellular and extracellular mechanisms. The intracellular mechanism involves the inhibition of pro-survival pathways and the activation of Fas-mediated apoptosis, while the extracellular mechanism involves the binding of a secreted form of this protein to glucose regulated protein 78 (GRP78) on the cell surface, which leads to activation of the extrinsic apoptotic pathway. This gene is located on the unstable human chromosomal 12q21 region and is often deleted or mutated different tumors. The encoded protein also plays an important role in the progression of age-related diseases. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAWR	NM_002583.4	c.*513T>G		3_prime_UTR_variant	7/7	ENST00000328827.9
PAWR	NM_001354732.2	c.*513T>G		3_prime_UTR_variant	7/7
PAWR	XM_047428916.1	c.*513T>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAWR	ENST00000328827.9	c.*513T>G		3_prime_UTR_variant	7/7	1	NM_002583.4	P1
PAWR	ENST00000550603.1	c.212+517T>G		intron_variant		5
PAWR	ENST00000548075.5	n.503+517T>G		intron_variant, non_coding_transcript_variant		4
PAWR	ENST00000549050.1	n.58-1813T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52666 AN: 151934 Hom.: 15340 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.0903 AC: 41 AN: 454 Hom.: 1 Cov.: 0 AF XY: 0.0956 AC XY: 26 AN XY: 272

Gnomad4 FIN exome AF: 0.0869

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.347 AC: 52779 AN: 152052 Hom.: 15396 Cov.: 32 AF XY: 0.339 AC XY: 25221 AN XY: 74322

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0938

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.318

Alfa AF: 0.261 Hom.: 2063

Bravo AF: 0.381

Asia WGS AF: 0.290 AC: 1005 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.7
DANN	Benign	0.73

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: rs2307220; hg19: chr12-79985874;