rs771471684

Variant names:

• chr1-156623915-G-C
• rs771471684
• NM_021817.3:c.194G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-156623915-G-C
• chr1-156623915-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021817.3(HAPLN2):​c.194G>C​(p.Ser65Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,604,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: HAPLN2 NM_021817.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.08
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAPLN2	NM_021817.3	MANE Select	c.194G>C	p.Ser65Thr	missense	Exon 4 of 7	NP_068589.1	Q9GZV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAPLN2	ENST00000255039.6	TSL:1 MANE Select	c.194G>C	p.Ser65Thr	missense	Exon 4 of 7	ENSP00000255039.1	Q9GZV7
	HAPLN2	ENST00000858239.1		c.236G>C	p.Ser79Thr	missense	Exon 4 of 7	ENSP00000528298.1
	HAPLN2	ENST00000968562.1		c.236G>C	p.Ser79Thr	missense	Exon 4 of 7	ENSP00000638621.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000432 AC: 10 AN: 231494 AF XY: 0.0000473

Gnomad AFR exome AF: 0.000139

Gnomad AMR exome AF: 0.000181

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000970

Gnomad OTH exome AF: 0.000177

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1451940 Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8 AN XY: 721532

African (AFR) AF: 0.000240 AC: 8 AN: 33356

American (AMR) AF: 0.000183 AC: 8 AN: 43746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25370

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 84500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107390

Other (OTH) AF: 0.00 AC: 0 AN: 59980

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74362

African (AFR) AF: 0.0000724 AC: 3 AN: 41462

American (AMR) AF: 0.000196 AC: 3 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000314 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.1
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.039
Sift	Benign	0.44	T
Sift4G	Benign	0.59	T
Polyphen		0.036	B
Vest4		0.22
MVP		0.50
MPC		1.4
ClinPred		0.27	T
GERP RS		4.1
Varity_R		0.092
gMVP		0.33
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: 8

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs771471684; hg19: chr1-156593707;