rs9622979

Variant names:

• chr22-39233604-G-A
• rs9622979
• NM_002608.4:c.161-80C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002608.4(PDGFB):​c.161-80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 978,628 control chromosomes in the GnomAD database, including 3,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1088 hom., cov: 32)
  • Exomes 𝑓: 0.062 (2312 hom.)
• Consequence: PDGFB NM_002608.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.66
• Publications: 8 publications found

Genes affected

PDGFB (HGNC:8800): (platelet derived growth factor subunit B) This gene encodes a member of the protein family comprised of both platelet-derived growth factors (PDGF) and vascular endothelial growth factors (VEGF). The encoded preproprotein is proteolytically processed to generate platelet-derived growth factor subunit B, which can homodimerize, or alternatively, heterodimerize with the related platelet-derived growth factor subunit A. These proteins bind and activate PDGF receptor tyrosine kinases, which play a role in a wide range of developmental processes. Mutations in this gene are associated with meningioma. Reciprocal translocations between chromosomes 22 and 17, at sites where this gene and that for collagen type 1, alpha 1 are located, are associated with dermatofibrosarcoma protuberans, a rare skin tumor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

PDGFB Gene-Disease associations (from GenCC):

• basal ganglia calcification, idiopathic, 5

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial meningioma

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-39233604-G-A is Benign according to our data. Variant chr22-39233604-G-A is described in ClinVar as Benign. ClinVar VariationId is 1262479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDGFB	NM_002608.4	c.161-80C>T		intron_variant	Intron 2 of 6	ENST00000331163.11	NP_002599.1
PDGFB	NM_033016.3	c.116-80C>T		intron_variant	Intron 2 of 6		NP_148937.1
PDGFB	XM_047441393.1	c.68-80C>T		intron_variant	Intron 2 of 6		XP_047297349.1
PDGFB	XM_047441394.1	c.68-80C>T		intron_variant	Intron 2 of 6		XP_047297350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDGFB	ENST00000331163.11	c.161-80C>T		intron_variant	Intron 2 of 6	1	NM_002608.4	ENSP00000330382.6
PDGFB	ENST00000381551.8	c.116-80C>T		intron_variant	Intron 2 of 6	5		ENSP00000370963.4
PDGFB	ENST00000455790.5	c.68-80C>T		intron_variant	Intron 2 of 4	4		ENSP00000402306.1
PDGFB	ENST00000440375.1	c.68-80C>T		intron_variant	Intron 2 of 4	4		ENSP00000405780.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15549 AN: 152000 Hom.: 1076 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0962

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0525

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0617 AC: 50998 AN: 826510 Hom.: 2312 AF XY: 0.0648 AC XY: 27562 AN XY: 425290

African (AFR) AF: 0.192 AC: 3406 AN: 17696

American (AMR) AF: 0.124 AC: 2952 AN: 23744

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 1741 AN: 17318

East Asian (EAS) AF: 0.0445 AC: 1413 AN: 31760

South Asian (SAS) AF: 0.151 AC: 8619 AN: 57162

European-Finnish (FIN) AF: 0.0434 AC: 1922 AN: 44300

Middle Eastern (MID) AF: 0.107 AC: 416 AN: 3878

European-Non Finnish (NFE) AF: 0.0468 AC: 27706 AN: 592182

Other (OTH) AF: 0.0734 AC: 2823 AN: 38470

GnomAD4 genome AF: 0.103 AC: 15607 AN: 152118 Hom.: 1088 Cov.: 32 AF XY: 0.103 AC XY: 7667 AN XY: 74380

African (AFR) AF: 0.191 AC: 7910 AN: 41460

American (AMR) AF: 0.122 AC: 1861 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 334 AN: 3472

East Asian (EAS) AF: 0.0800 AC: 412 AN: 5150

South Asian (SAS) AF: 0.156 AC: 750 AN: 4822

European-Finnish (FIN) AF: 0.0435 AC: 461 AN: 10606

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0525 AC: 3569 AN: 68002

Other (OTH) AF: 0.108 AC: 228 AN: 2112

Alfa AF: 0.0688 Hom.: 432

Bravo AF: 0.107

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.037
DANN	Benign	0.68
PhyloP100		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9622979; hg19: chr22-39629609;