Variant 19-4493812-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001520.3(HDGFL2):c.788C>T(p.Ser263Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,538,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

HDGFL2
NM_001001520.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08798671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDGFL2	NM_001001520.3 linkuse as main transcript	c.788C>T	p.Ser263Phe	missense_variant	7/16	ENST00000616600.5	NP_001001520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HDGFL2	ENST00000616600.5 linkuse as main transcript	c.788C>T	p.Ser263Phe	missense_variant	7/16	1	NM_001001520.3	ENSP00000483345.1	Q7Z4V5-1
HDGFL2	ENST00000621835.4 linkuse as main transcript	c.788C>T	p.Ser263Phe	missense_variant	7/16	1		ENSP00000483702.1	Q7Z4V5-2
HDGFL2	ENST00000615225.1 linkuse as main transcript	n.641C>T		non_coding_transcript_exon_variant	6/15	5		ENSP00000477592.1	A0A087WT54
HDGFL2	ENST00000589486.5 linkuse as main transcript	c.*50C>T		downstream_gene_variant		5		ENSP00000465267.1	K7EJP7

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD4 exome

AF:

0.00000793

AC:

AN:

1386442

Hom.:

Cov.:

AF XY:

0.00000733

AC XY:

AN XY:

682176

show subpopulations

Gnomad4 AFR exome

AF:

0.000289

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000190

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

The c.788C>T (p.S263F) alteration is located in exon 7 (coding exon 7) of the HDGFRP2 gene. This alteration results from a C to T substitution at nucleotide position 788, causing the serine (S) at amino acid position 263 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

L;L

PrimateAI

Uncertain

0.73

Sift4G

Uncertain

0.051

T;T

Polyphen

0.0

B;.

Vest4

0.23

MVP

0.043

ClinPred

0.44

GERP RS

2.7

Varity_R

0.064

gMVP

0.12

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

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