Variant chr19-4499600-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001001520.3(HDGFL2):c.1685A>G(p.Asn562Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,609,868 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 23 hom. )

Consequence

HDGFL2
NM_001001520.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.271

Variant links:

Genes affected

HDGFL2 (HGNC:14680): (HDGF like 2) This gene encodes a member of the hepatoma-derived growth factor (HDGF) family. The protein includes an N-terminal PWWP domain that binds to methyl-lysine-containing histones, with specific binding of this protein to tri-methylated lysines 36 and 79 of histone H3, and di- and tri-methylated lysine 20 of histone H4. The protein functions in LEDGF/p75-independent HIV-1 replication by determining HIV-1 integration site selection. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2014]

HDGFL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 19-4499600-A-G is Benign according to our data. Variant chr19-4499600-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3024805.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDGFL2	NM_001001520.3 linkuse as main transcript	c.1685A>G	p.Asn562Ser	missense_variant	14/16	ENST00000616600.5	NP_001001520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDGFL2	ENST00000616600.5 linkuse as main transcript	c.1685A>G	p.Asn562Ser	missense_variant	14/16	1	NM_001001520.3	ENSP00000483345.1		Q7Z4V5-1

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

466

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00433

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00377

AC:

901

AN:

239154

Hom.:

AF XY:

0.00392

AC XY:

509

AN XY:

129884

show subpopulations

Gnomad AFR exome

AF:

0.000421

Gnomad AMR exome

AF:

0.00333

Gnomad ASJ exome

AF:

0.0230

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.000341

Gnomad NFE exome

AF:

0.00455

Gnomad OTH exome

AF:

0.00475

GnomAD4 exome

AF:

0.00415

AC:

6050

AN:

1457688

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

3030

AN XY:

724662

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00334

Gnomad4 ASJ exome

AF:

0.0237

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00135

Gnomad4 FIN exome

AF:

0.000378

Gnomad4 NFE exome

AF:

0.00430

Gnomad4 OTH exome

AF:

0.00524

GnomAD4 genome

AF:

0.00306

AC:

466

AN:

152180

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00433

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00523

Hom.:

Bravo

AF:

0.00355

ESP6500AA

AF:

0.000773

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00321

AC:

388

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

HDGFL2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.4

DANN

Benign

0.69

DEOGEN2

Benign

0.033

T;.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Benign

0.28

Sift4G

Uncertain

0.032

D;D;T

Polyphen

0.0010

B;B;.

Vest4

0.15

MVP

0.043

ClinPred

0.00031

GERP RS

0.75

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.016

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.27

Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over