Genetic Variant HAPLN2:c.-166+123C>T (chr1-156619658-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_021817.3(HAPLN2):c.-166+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,924 control chromosomes in the GnomAD database, including 4,856 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 0.25 ( 4851 hom., cov: 30)

Exomes 𝑓: 0.35 ( 5 hom. )

Consequence

HAPLN2
NM_021817.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0310

Publications

17 publications found

Variant links:

Genes affected

HAPLN2 (HGNC:17410): (hyaluronan and proteoglycan link protein 2) Predicted to enable hyaluronic acid binding activity. Predicted to be involved in central nervous system development and skeletal system development. Predicted to act upstream of or within establishment of blood-nerve barrier and extracellular matrix assembly. Predicted to be located in extracellular region. Predicted to be active in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

HAPLN2 links:

BCAN-AS2 (HGNC:56267): (BCAN antisense RNA 2)

BCAN-AS2 links:

LOC101928177 (HGNC:):

LOC101928177 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=-0.77).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAPLN2	NM_021817.3 link	c.-166+123C>T		intron_variant	Intron 1 of 6	ENST00000255039.6	NP_068589.1	Q9GZV7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAPLN2	ENST00000255039.6 link	c.-166+123C>T		intron_variant	Intron 1 of 6	1	NM_021817.3	ENSP00000255039.1		Q9GZV7

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37428

AN:

151744

Hom.:

4837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.363

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.265

GnomAD4 exome

AF:

0.350

AC:

AN:

Hom.:

AF XY:

0.357

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

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:

0.375

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.326

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.247

AC:

37476

AN:

151864

Hom.:

4851

Cov.:

AF XY:

0.250

AC XY:

18591

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.217

AC:

8976

AN:

41416

American (AMR)

AF:

0.264

AC:

4019

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

960

AN:

3470

East Asian (EAS)

AF:

0.363

AC:

1861

AN:

5126

South Asian (SAS)

AF:

0.489

AC:

2342

AN:

4792

European-Finnish (FIN)

AF:

0.213

AC:

2259

AN:

10584

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16223

AN:

67912

Other (OTH)

AF:

0.272

AC:

573

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1375

2749

4124

5498

6873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.257

Hom.:

2735

Bravo

AF:

0.243

Asia WGS

AF:

0.451

AC:

1569

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.6

(source)

DANN

Benign

0.78

PhyloP100

0.031

PromoterAI

-0.019

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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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