4-54229547-T-G

Variant names:

• chr4-54229547-T-G
• rs74962312
• NM_006206.6:c.-13+132T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006206.6(PDGFRA):​c.-13+132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 390,056 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (3 hom.)
• Consequence: PDGFRA NM_006206.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.168
• Publications: 0 publications found

Genes affected

PDGFRA (HGNC:8803): (platelet derived growth factor receptor alpha) This gene encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family. These growth factors are mitogens for cells of mesenchymal origin. The identity of the growth factor bound to a receptor monomer determines whether the functional receptor is a homodimer or a heterodimer, composed of both platelet-derived growth factor receptor alpha and beta polypeptides. Studies suggest that this gene plays a role in organ development, wound healing, and tumor progression. Mutations in this gene have been associated with idiopathic hypereosinophilic syndrome, somatic and familial gastrointestinal stromal tumors, and a variety of other cancers. [provided by RefSeq, Mar 2012]

PDGFRA Gene-Disease associations (from GenCC):

• gastrointestinal stromal tumor

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• polyps, multiple and recurrent inflammatory fibroid, gastrointestinal

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• isolated cleft palate

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

ENSG00000282278 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-54229547-T-G is Benign according to our data. Variant chr4-54229547-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1302476.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00691 (1041/150584) while in subpopulation AFR AF = 0.0239 (981/41126). AF 95% confidence interval is 0.0226. There are 8 homozygotes in GnomAd4. There are 501 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1041 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006206.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	NM_006206.6	MANE Select	c.-13+132T>G		intron	N/A	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.-16+132T>G		intron	N/A	NP_001334757.1
	PDGFRA	NM_001347827.2		c.-13+132T>G		intron	N/A	NP_001334756.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.-13+132T>G		intron	N/A	ENSP00000257290.5	P16234-1
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-45378T>G		intron	N/A	ENSP00000423325.1	A0A0B4J203
	PDGFRA	ENST00000508170.5	TSL:1	c.-13+132T>G		intron	N/A	ENSP00000425648.1	P16234-2

Frequencies

GnomAD3 genomes AF: 0.00692 AC: 1042 AN: 150520 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00252

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00433

GnomAD4 exome AF: 0.00101 AC: 242 AN: 239472 Hom.: 3 AF XY: 0.000913 AC XY: 111 AN XY: 121524

African (AFR) AF: 0.0247 AC: 173 AN: 6998

American (AMR) AF: 0.00248 AC: 18 AN: 7244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9014

East Asian (EAS) AF: 0.00 AC: 0 AN: 22400

South Asian (SAS) AF: 0.00 AC: 0 AN: 2132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20040

Middle Eastern (MID) AF: 0.00159 AC: 2 AN: 1254

European-Non Finnish (NFE) AF: 0.0000971 AC: 15 AN: 154470

Other (OTH) AF: 0.00214 AC: 34 AN: 15920

GnomAD4 genome AF: 0.00691 AC: 1041 AN: 150584 Hom.: 8 Cov.: 31 AF XY: 0.00682 AC XY: 501 AN XY: 73462

African (AFR) AF: 0.0239 AC: 981 AN: 41126

American (AMR) AF: 0.00251 AC: 38 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.000417 AC: 2 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67714

Other (OTH) AF: 0.00429 AC: 9 AN: 2096

Alfa AF: 0.00691 Hom.: 2

Bravo AF: 0.00796

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		0.17
PromoterAI		-0.034	Neutral
Mutation Taster		=100/0	polymorphism

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: rs74962312; hg19: chr4-55095714;