Genetic Variant ENST00000452365.2:n.4082G>C (chr2-176173103-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000452365.2(HAGLR):n.4082G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,522 control chromosomes in the GnomAD database, including 45,068 homozygotes. 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 0.76 ( 44964 hom., cov: 34)

Exomes 𝑓: 0.72 ( 104 hom. )

Consequence

HAGLR
ENST00000452365.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.13

Publications

10 publications found

Variant links:

Genes affected

HAGLR (HGNC:43755): (HOXD antisense growth-associated long non-coding RNA)

HAGLR links:

HOXD3 (HGNC:5137): (homeobox D3) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located at 2q31-2q37 chromosome regions. Deletions that removed the entire HOXD gene cluster or 5' end of this cluster have been associated with severe limb and genital abnormalities. The protein encoded by this gene may play a role in the regulation of cell adhesion processes. [provided by RefSeq, Jul 2008]

HOXD3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000452365.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HOXD3	NM_006898.5	MANE Select	c.*829C>G	downstream_gene	N/A	NP_008829.3
HAGLR	NR_033979.2		n.*86G>C	downstream_gene	N/A
HAGLR	NR_110458.1		n.*86G>C	downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
HAGLR	ENST00000452365.2	TSL:4	n.4082G>C	non_coding_transcript_exon	Exon 5 of 5
HAGLR	ENST00000669485.1		n.3970G>C	non_coding_transcript_exon	Exon 4 of 4
HAGLR	ENST00000413969.6	TSL:3	n.406+3432G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.763

AC:

115916

AN:

151994

Hom.:

44899

Cov.:

show subpopulations

Gnomad AFR

AF:

0.893

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.791

Gnomad ASJ

AF:

0.704

Gnomad EAS

AF:

0.761

Gnomad SAS

AF:

0.846

Gnomad FIN

AF:

0.711

Gnomad MID

AF:

0.761

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.765

GnomAD4 exome

AF:

0.717

AC:

294

AN:

410

Hom.:

104

Cov.:

AF XY:

0.707

AC XY:

174

AN XY:

246

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.713

AC:

288

AN:

404

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.763

AC:

116039

AN:

152112

Hom.:

44964

Cov.:

AF XY:

0.766

AC XY:

56955

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.894

AC:

37095

AN:

41512

American (AMR)

AF:

0.791

AC:

12090

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

2443

AN:

3472

East Asian (EAS)

AF:

0.761

AC:

3926

AN:

5160

South Asian (SAS)

AF:

0.847

AC:

4084

AN:

4824

European-Finnish (FIN)

AF:

0.711

AC:

7513

AN:

10564

Middle Eastern (MID)

AF:

0.767

AC:

224

AN:

292

European-Non Finnish (NFE)

AF:

0.682

AC:

46391

AN:

67988

Other (OTH)

AF:

0.764

AC:

1613

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1420

2840

4261

5681

7101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<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:

0.730

Hom.:

5098

Bravo

AF:

0.774

Asia WGS

AF:

0.805

AC:

2802

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

3.1

Mutation Taster

=92/8

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over