dbSNP rs17085310: KDR:n.2015C>T (chr4-55104615-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000512566.1(KDR):n.2015C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,580,432 control chromosomes in the GnomAD database, including 709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.014 ( 73 hom., cov: 32)

Exomes 𝑓: 0.011 ( 636 hom. )

Consequence

KDR
ENST00000512566.1 non_coding_transcript_exon

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.658

Publications

5 publications found

Variant links:

Genes affected

KDR (HGNC:6307): (kinase insert domain receptor) Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes one of the two receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis and sprouting. The signalling and trafficking of this receptor are regulated by multiple factors, including Rab GTPase, P2Y purine nucleotide receptor, integrin alphaVbeta3, T-cell protein tyrosine phosphatase, etc.. Mutations of this gene are implicated in infantile capillary hemangiomas. [provided by RefSeq, May 2009]

KDR Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

KDR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4 link	c.1987+28C>T		intron_variant	Intron 13 of 29	ENST00000263923.5	NP_002244.1	P35968-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KDR	ENST00000512566.1 link	n.2015C>T	non_coding_transcript_exon_variant	Exon 13 of 13	1
KDR	ENST00000263923.5 link	c.1987+28C>T	intron_variant	Intron 13 of 29	1	NM_002253.4	ENSP00000263923.4	P35968-1
KDR	ENST00000647068.1 link	n.2000+28C>T	intron_variant	Intron 13 of 29

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2072

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0574

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0853

Gnomad SAS

AF:

0.0457

Gnomad FIN

AF:

0.0197

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00318

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0303

AC:

7393

AN:

244128

AF XY:

0.0262

show subpopulations

Gnomad AFR exome

AF:

0.00175

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.0870

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.00396

Gnomad OTH exome

AF:

0.0186

GnomAD4 exome

AF:

0.0110

AC:

15678

AN:

1428186

Hom.:

636

Cov.:

AF XY:

0.0109

AC XY:

7780

AN XY:

712138

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

32790

American (AMR)

AF:

0.108

AC:

4789

AN:

44186

Ashkenazi Jewish (ASJ)

AF:

0.00190

AC:

AN:

25846

East Asian (EAS)

AF:

0.0956

AC:

3768

AN:

39408

South Asian (SAS)

AF:

0.0308

AC:

2612

AN:

84890

European-Finnish (FIN)

AF:

0.0197

AC:

1029

AN:

52202

Middle Eastern (MID)

AF:

0.00245

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00235

AC:

2549

AN:

1083862

Other (OTH)

AF:

0.0140

AC:

831

AN:

59282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

770

1540

2311

3081

3851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0136

AC:

2069

AN:

152246

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1149

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00178

AC:

AN:

41546

American (AMR)

AF:

0.0572

AC:

875

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3470

East Asian (EAS)

AF:

0.0855

AC:

442

AN:

5168

South Asian (SAS)

AF:

0.0452

AC:

218

AN:

4828

European-Finnish (FIN)

AF:

0.0197

AC:

209

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00318

AC:

216

AN:

68016

Other (OTH)

AF:

0.0118

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

101

203

304

406

507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.0700

AC:

242

AN:

3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.23

(source)

DANN

Benign

0.41

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over