Genetic Variant HDGF:p.Glu216Lys (chr1-156743722-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004494.3(HDGF):c.646G>A(p.Glu216Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,603,594 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 1 hom. )

Consequence

HDGF
NM_004494.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

Publications

0 publications found

Variant links:

Genes affected

HDGF (HGNC:4856): (heparin binding growth factor) This gene encodes a member of the hepatoma-derived growth factor family. The encoded protein has mitogenic and DNA-binding activity and may play a role in cellular proliferation and differentiation. High levels of expression of this gene enhance the growth of many tumors. This gene was thought initially to be located on chromosome X; however, that location has been determined to correspond to a related pseudogene. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2016]

HDGF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15593132).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004494.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDGF	NM_004494.3	MANE Select	c.646G>A	p.Glu216Lys	missense	Exon 5 of 6	NP_004485.1	P51858-1
HDGF	NM_001319186.2		c.715G>A	p.Glu239Lys	missense	Exon 5 of 6	NP_001306115.1
HDGF	NM_001126050.2		c.694G>A	p.Glu232Lys	missense	Exon 5 of 6	NP_001119522.1	P51858-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDGF	ENST00000357325.10	TSL:1 MANE Select	c.646G>A	p.Glu216Lys	missense	Exon 5 of 6	ENSP00000349878.5	P51858-1
HDGF	ENST00000465180.5	TSL:1	n.1060G>A		non_coding_transcript_exon	Exon 7 of 8
HDGF	ENST00000710272.1		c.901G>A	p.Glu301Lys	missense	Exon 5 of 6	ENSP00000518165.1	A0AA34QVG5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000212

AC:

AN:

235580

AF XY:

0.0000312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000286

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1451398

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

721808

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32982

American (AMR)

AF:

0.0000234

AC:

AN:

42792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25308

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53062

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1107136

Other (OTH)

AF:

0.0000167

AC:

AN:

59840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000131

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000108

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

M_CAP

Benign

0.0059

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

2.7

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.70

REVEL

Benign

0.052

Sift

Benign

0.14

Sift4G

Benign

0.34

Polyphen

0.079

Vest4

0.41

MutPred

0.13

Gain of ubiquitination at E216 (P = 0.0075)

MVP

0.52

MPC

0.52

ClinPred

0.11

GERP RS

4.7

Varity_R

0.096

gMVP

0.17

Mutation Taster

=89/11

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over