chr1-156624864-C-A

Variant names:

• chr1-156624864-C-A
• rs12567958
• NM_021817.3:c.739+81C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 21 publications found

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]

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

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAPLN2	NM_021817.3	c.739+81C>A		intron_variant	Intron 6 of 6	ENST00000255039.6	NP_068589.1
HAPLN2	XM_011509853.3	c.739+81C>A		intron_variant	Intron 6 of 6		XP_011508155.1
HAPLN2	XM_017002020.2	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	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.: 29

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

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

GnomAD4 genome AF: 0.580 AC: 87998 AN: 151708 Hom.: 28488 Cov.: 29 AF XY: 0.580 AC XY: 42942 AN XY: 74092

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

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
DANN	Benign	0.64
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12567958; hg19: chr1-156594656;