dbSNP rs12567958: HAPLN2:c.739+81C>A (chr1-156624864-C-A) – 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.739+81C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,406,302 control chromosomes in the GnomAD database, including 341,969 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 0.58 ( 28488 hom., cov: 29)

Exomes 𝑓: 0.70 ( 313481 hom. )

Consequence

HAPLN2
NM_021817.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.446

Publications

21 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:

Genome browser will be placed here

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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
HAPLN2	NM_021817.3 link	c.739+81C>A	intron_variant	Intron 6 of 6	ENST00000255039.6	NP_068589.1
HAPLN2	XM_011509853.3 link	c.739+81C>A	intron_variant	Intron 6 of 6		XP_011508155.1
HAPLN2	XM_017002020.2 link	c.739+81C>A	intron_variant	Intron 7 of 7		XP_016857509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAPLN2	ENST00000255039.6 link	c.739+81C>A		intron_variant	Intron 6 of 6	1	NM_021817.3	ENSP00000255039.1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

87974

AN:

151598

Hom.:

28483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.696

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.694

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.419

Gnomad FIN

AF:

0.763

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.725

Gnomad OTH

AF:

0.602

GnomAD4 exome

AF:

0.699

AC:

876988

AN:

1254594

Hom.:

313481

AF XY:

0.693

AC XY:

422634

AN XY:

610258

show subpopulations

African (AFR)

AF:

0.258

AC:

7055

AN:

27376

American (AMR)

AF:

0.667

AC:

13691

AN:

20514

Ashkenazi Jewish (ASJ)

AF:

0.683

AC:

12711

AN:

18616

East Asian (EAS)

AF:

0.523

AC:

17865

AN:

34160

South Asian (SAS)

AF:

0.434

AC:

27331

AN:

62906

European-Finnish (FIN)

AF:

0.749

AC:

22399

AN:

29918

Middle Eastern (MID)

AF:

0.588

AC:

2161

AN:

3674

European-Non Finnish (NFE)

AF:

0.736

AC:

739350

AN:

1005064

Other (OTH)

AF:

0.657

AC:

34425

AN:

52366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

13160

26320

39479

52639

65799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18770

37540

56310

75080

93850

<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:

0.580

AC:

87998

AN:

151708

Hom.:

28488

Cov.:

AF XY:

0.580

AC XY:

42942

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.277

AC:

11451

AN:

41408

American (AMR)

AF:

0.655

AC:

9984

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.694

AC:

2409

AN:

3470

East Asian (EAS)

AF:

0.567

AC:

2894

AN:

5108

South Asian (SAS)

AF:

0.420

AC:

2022

AN:

4816

European-Finnish (FIN)

AF:

0.763

AC:

8003

AN:

10492

Middle Eastern (MID)

AF:

0.592

AC:

174

AN:

294

European-Non Finnish (NFE)

AF:

0.725

AC:

49174

AN:

67858

Other (OTH)

AF:

0.595

AC:

1254

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1586

3171

4757

6342

7928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.677

Hom.:

59437

Bravo

AF:

0.568

Asia WGS

AF:

0.429

AC:

1488

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.8

(source)

DANN

Benign

0.64

PhyloP100

-0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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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