rs577939683

Positions:

• chr3-167713274-CAA-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_007217.4(PDCD10):​c.96+6786_96+6787del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 152,046 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.0030 (2 hom., cov: 32)
• Consequence: PDCD10 NM_007217.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.303

Genes affected

PDCD10 (HGNC:8761): (programmed cell death 10) This gene encodes an evolutionarily conserved protein associated with cell apoptosis. The protein interacts with the serine/threonine protein kinase MST4 to modulate the extracellular signal-regulated kinase (ERK) pathway. It also interacts with and is phosphoryated by serine/threonine kinase 25, and is thought to function in a signaling pathway essential for vascular developent. Mutations in this gene are one cause of cerebral cavernous malformations, which are vascular malformations that cause seizures and cerebral hemorrhages. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00299 (454/152046) while in subpopulation AMR AF= 0.00504 (77/15272). AF 95% confidence interval is 0.00429. There are 2 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 454 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD10	NM_007217.4	c.96+6786_96+6787del		intron_variant		ENST00000392750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD10	ENST00000392750.7	c.96+6786_96+6787del		intron_variant		1	NM_007217.4	P1

Frequencies

GnomAD3 genomes AF: 0.00299 AC: 454 AN: 151930 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00505

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00472

Gnomad OTH AF: 0.00336

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

GnomAD4 genome AF: 0.00299 AC: 454 AN: 152046 Hom.: 2 Cov.: 32 AF XY: 0.00283 AC XY: 210 AN XY: 74336

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.00504

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00472

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00108 Hom.: 0

Bravo AF: 0.00314

Asia WGS AF: 0.00116 AC: 4 AN: 3474

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Cerebral cavernous malformation 3 Other:1

not provided, no classification provided

research

Institute of Human Genetics Greifswald, Research Division, University Medicine Greifswald

May 15, 2017

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Computational scores

Source: dbNSFP v4.3

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: rs577939683; hg19: chr3-167431062;