Genetic Variant HDGFL2:c.*179T>G (chr19-4502189-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001520.3(HDGFL2):c.*179T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000251 in 678,536 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Consequence

HDGFL2
NM_001001520.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.91

Publications

34 publications found

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:

PLIN4 (HGNC:29393): (perilipin 4) Members of the perilipin family, such as PLIN4, coat intracellular lipid storage droplets (Wolins et al., 2003 [PubMed 12840023]).[supplied by OMIM, Feb 2010]

PLIN4 Gene-Disease associations (from GenCC):

vacuolar Neuromyopathy
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

PLIN4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDGFL2	NM_001001520.3 link	c.*179T>G		3_prime_UTR_variant	Exon 16 of 16	ENST00000616600.5	NP_001001520.1
PLIN4	NM_001367868.2 link	c.*2270A>C		downstream_gene_variant		ENST00000301286.5	NP_001354797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDGFL2	ENST00000616600.5 link	c.*179T>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_001001520.3	ENSP00000483345.1		Q7Z4V5-1
PLIN4	ENST00000301286.5 link	c.*2270A>C		downstream_gene_variant		5	NM_001367868.2	ENSP00000301286.4		Q96Q06

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000176

AC:

AN:

113682

AF XY:

0.0000323

show subpopulations

Gnomad AFR exome

AF:

0.000337

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000949

AC:

AN:

526620

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

285920

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

13828

American (AMR)

AF:

0.00

AC:

AN:

26528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19410

East Asian (EAS)

AF:

0.00

AC:

AN:

31780

South Asian (SAS)

AF:

0.00

AC:

AN:

56560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3974

European-Non Finnish (NFE)

AF:

0.00000321

AC:

AN:

311788

Other (OTH)

AF:

0.00

AC:

AN:

29568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000790

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

41346

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

84574

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

2.9

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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19-4502189-T-G

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