rs151259376

Variant names:

• chr4-54264962-G-A
• rs151259376
• NM_006206.6:c.672G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-54264962-G-A
• chr4-54264962-G-C
• chr4-54264962-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_006206.6(PDGFRA):​c.672G>A​(p.Val224Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,613,306 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (8 hom.)
• Consequence: PDGFRA NM_006206.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.786
• Publications: 4 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 4-54264962-G-A is Benign according to our data. Variant chr4-54264962-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 348895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.786 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00649 (987/152140) while in subpopulation AFR AF = 0.0216 (897/41512). AF 95% confidence interval is 0.0204. There are 8 homozygotes in GnomAd4. There are 497 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 987 AD,Unknown 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.672G>A	p.Val224Val	synonymous	Exon 5 of 23	NP_006197.1	P16234-1
	PDGFRA	NM_001347828.2		c.747G>A	p.Val249Val	synonymous	Exon 6 of 24	NP_001334757.1
	PDGFRA	NM_001347830.2		c.711G>A	p.Val237Val	synonymous	Exon 5 of 23	NP_001334759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDGFRA	ENST00000257290.10	TSL:1 MANE Select	c.672G>A	p.Val224Val	synonymous	Exon 5 of 23	ENSP00000257290.5	P16234-1
	PDGFRA	ENST00000508170.5	TSL:1	c.*1006G>A		3_prime_UTR	Exon 4 of 4	ENSP00000425648.1	P16234-2
	ENSG00000282278	ENST00000507166.5	TSL:2	c.1018-9963G>A		intron	N/A	ENSP00000423325.1	A0A0B4J203

Frequencies

GnomAD3 genomes AF: 0.00647 AC: 983 AN: 152022 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00187 AC: 470 AN: 251440 AF XY: 0.00135

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000728 AC: 1063 AN: 1461166 Hom.: 8 Cov.: 31 AF XY: 0.000622 AC XY: 452 AN XY: 726950

African (AFR) AF: 0.0232 AC: 775 AN: 33452

American (AMR) AF: 0.00195 AC: 87 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000927 AC: 103 AN: 1111402

Other (OTH) AF: 0.00151 AC: 91 AN: 60362

GnomAD4 genome AF: 0.00649 AC: 987 AN: 152140 Hom.: 8 Cov.: 32 AF XY: 0.00668 AC XY: 497 AN XY: 74370

African (AFR) AF: 0.0216 AC: 897 AN: 41512

American (AMR) AF: 0.00380 AC: 58 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68004

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.00631 Hom.: 10

Bravo AF: 0.00747

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Gastrointestinal stromal tumor (2)
-	-	2	not provided (2)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	Idiopathic hypereosinophilic syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.52
DANN	Benign	0.86
PhyloP100		-0.79
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs151259376; hg19: chr4-55131129; COSMIC: COSV104378167; COSMIC: COSV104378167;