dbSNP rs13109660: KDR:c.1987+130C>T (chr4-55104513-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 NM_002253.4(KDR):c.1987+130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 742,436 control chromosomes in the GnomAD database, including 44,324 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7746 hom., cov: 32)

Exomes 𝑓: 0.35 ( 36578 hom. )

Consequence

KDR
NM_002253.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.851

Publications

13 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=-0.99).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDR	NM_002253.4 link	c.1987+130C>T		intron_variant	Intron 13 of 29	ENST00000263923.5	NP_002244.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
KDR	ENST00000263923.5 link	c.1987+130C>T	intron_variant	Intron 13 of 29	1	NM_002253.4	ENSP00000263923.4
KDR	ENST00000647068.1 link	n.2000+130C>T	intron_variant	Intron 13 of 29
KDR	ENST00000512566.1 link	n.*80C>T	downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46077

AN:

151780

Hom.:

7729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.380

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.318

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.312

GnomAD4 exome

AF:

0.346

AC:

204132

AN:

590536

Hom.:

36578

AF XY:

0.343

AC XY:

107958

AN XY:

314494

show subpopulations

African (AFR)

AF:

0.148

AC:

2376

AN:

16106

American (AMR)

AF:

0.527

AC:

16488

AN:

31300

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

6176

AN:

19416

East Asian (EAS)

AF:

0.323

AC:

10379

AN:

32086

South Asian (SAS)

AF:

0.318

AC:

18957

AN:

59690

European-Finnish (FIN)

AF:

0.378

AC:

13409

AN:

35466

Middle Eastern (MID)

AF:

0.253

AC:

1025

AN:

4044

European-Non Finnish (NFE)

AF:

0.346

AC:

124974

AN:

360798

Other (OTH)

AF:

0.327

AC:

10348

AN:

31630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

6997

13994

20992

27989

34986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1378

2756

4134

5512

6890

<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:

0.304

AC:

46112

AN:

151900

Hom.:

7746

Cov.:

AF XY:

0.307

AC XY:

22787

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.149

AC:

6182

AN:

41414

American (AMR)

AF:

0.457

AC:

6982

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

1104

AN:

3470

East Asian (EAS)

AF:

0.307

AC:

1582

AN:

5156

South Asian (SAS)

AF:

0.308

AC:

1477

AN:

4798

European-Finnish (FIN)

AF:

0.369

AC:

3879

AN:

10522

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.351

AC:

23839

AN:

67944

Other (OTH)

AF:

0.309

AC:

651

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1594

3189

4783

6378

7972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.320

Hom.:

3247

Bravo

AF:

0.306

Asia WGS

AF:

0.270

AC:

937

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.013

(source)

DANN

Benign

0.62

PhyloP100

-0.85

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

Computational scores

Splicing

Publications

Other links and lift over