rs12567958

Positions:

• chr1-156624864-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HAPLN2	NM_021817.3	c.739+81C>A		intron_variant		ENST00000255039.6
HAPLN2	XM_011509853.3	c.739+81C>A		intron_variant
HAPLN2	XM_017002020.2	c.739+81C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAPLN2	ENST00000255039.6	c.739+81C>A		intron_variant		1	NM_021817.3	P1
HAPLN2	ENST00000494218.1	n.587+81C>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.523

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.736

Gnomad4 OTH exome AF: 0.657

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

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.595

Alfa AF: 0.690 Hom.: 48366

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

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

Other links and lift over

dbSNP: rs12567958; hg19: chr1-156594656;