Variant 19-4494212-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001001520.3(HDGFL2):c.961G>A(p.Glu321Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000305 in 1,312,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

HDGFL2
NM_001001520.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.74

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27431977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDGFL2	NM_001001520.3 linkuse as main transcript	c.961G>A	p.Glu321Lys	missense_variant	9/16	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.961G>A	p.Glu321Lys	missense_variant	9/16	1	NM_001001520.3	ENSP00000483345.1	Q7Z4V5-1
HDGFL2	ENST00000621835.4 linkuse as main transcript	c.961G>A	p.Glu321Lys	missense_variant	9/16	1		ENSP00000483702.1	Q7Z4V5-2
HDGFL2	ENST00000615225.1 linkuse as main transcript	n.814G>A		non_coding_transcript_exon_variant	8/15	5		ENSP00000477592.1	A0A087WT54

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000323

AC:

AN:

61882

Hom.:

AF XY:

0.0000594

AC XY:

AN XY:

33674

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000180

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000305

AC:

AN:

1312518

Hom.:

Cov.:

AF XY:

0.00000467

AC XY:

AN XY:

642080

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000931

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.58e-7

Gnomad4 OTH exome

AF:

0.0000185

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

Nov 09, 2021

The c.961G>A (p.E321K) alteration is located in exon 9 (coding exon 9) of the HDGFRP2 gene. This alteration results from a G to A substitution at nucleotide position 961, causing the glutamic acid (E) at amino acid position 321 to be replaced by a lysine (K). 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

Pathogenic

0.82

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.073

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Pathogenic

0.95

Sift4G

Benign

0.26

T;T

Polyphen

1.0

D;.

Vest4

0.43

MutPred

0.17

Gain of methylation at E321 (P = 0.0058);Gain of methylation at E321 (P = 0.0058);

MVP

0.15

ClinPred

0.76

GERP RS

4.4

Varity_R

0.36

gMVP

0.27

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