Variant chr1-156623497-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021817.3(HAPLN2):c.7G>A(p.Gly3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HAPLN2
NM_021817.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09279433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HAPLN2	NM_021817.3 linkuse as main transcript	c.7G>A	p.Gly3Ser	missense_variant	3/7	ENST00000255039.6
HAPLN2	XM_011509853.3 linkuse as main transcript	c.7G>A	p.Gly3Ser	missense_variant	3/7
HAPLN2	XM_017002020.2 linkuse as main transcript	c.7G>A	p.Gly3Ser	missense_variant	4/8
HAPLN2	XM_047427123.1 linkuse as main transcript	c.249G>A	p.Gln83=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HAPLN2	ENST00000255039.6 linkuse as main transcript	c.7G>A	p.Gly3Ser	missense_variant	3/7	1	NM_021817.3	P1
HAPLN2	ENST00000456112.1 linkuse as main transcript	c.7G>A	p.Gly3Ser	missense_variant	3/5	5
HAPLN2	ENST00000482204.1 linkuse as main transcript	n.262G>A		non_coding_transcript_exon_variant	3/3	2
HAPLN2	ENST00000487988.5 linkuse as main transcript	n.426G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251078

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2024

The c.7G>A (p.G3S) alteration is located in exon 3 (coding exon 1) of the HAPLN2 gene. This alteration results from a G to A substitution at nucleotide position 7, causing the glycine (G) at amino acid position 3 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.042

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.43

T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.065

Sift

Benign

0.21

T;T

Sift4G

Benign

0.084

T;T

Polyphen

0.0

B;.

Vest4

0.23

MutPred

0.38

Loss of catalytic residue at G3 (P = 0.0331);Loss of catalytic residue at G3 (P = 0.0331);

MVP

0.38

MPC

0.78

ClinPred

0.11

GERP RS

2.6

Varity_R

0.041

gMVP

0.28

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