Variant 1-156623562-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021817.3(HAPLN2):c.72C>T(p.Ala24=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,614,122 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

HAPLN2
NM_021817.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.395

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 1-156623562-C-T is Benign according to our data. Variant chr1-156623562-C-T is described in ClinVar as [Benign]. Clinvar id is 718728.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.395 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HAPLN2	NM_021817.3 linkuse as main transcript	c.72C>T	p.Ala24=	synonymous_variant	3/7	ENST00000255039.6
HAPLN2	XM_047427123.1 linkuse as main transcript	c.314C>T	p.Pro105Leu	missense_variant	4/5
HAPLN2	XM_011509853.3 linkuse as main transcript	c.72C>T	p.Ala24=	synonymous_variant	3/7
HAPLN2	XM_017002020.2 linkuse as main transcript	c.72C>T	p.Ala24=	synonymous_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HAPLN2	ENST00000255039.6 linkuse as main transcript	c.72C>T	p.Ala24=	synonymous_variant	3/7	1	NM_021817.3	P1
HAPLN2	ENST00000456112.1 linkuse as main transcript	c.72C>T	p.Ala24=	synonymous_variant	3/5	5
HAPLN2	ENST00000482204.1 linkuse as main transcript	n.327C>T		non_coding_transcript_exon_variant	3/3	2
HAPLN2	ENST00000487988.5 linkuse as main transcript	n.491C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

174

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00191

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00115

AC:

289

AN:

251086

Hom.:

AF XY:

0.00114

AC XY:

155

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000608

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00189

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00168

AC:

2456

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1205

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000615

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00114

AC:

174

AN:

152278

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00191

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00140

Hom.:

Bravo

AF:

0.00132

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00213

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.0

DANN

Benign

0.50

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