1-156623941-G-C

Position:

• chr1-156623941-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021817.3(HAPLN2):​c.220G>C​(p.Glu74Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HAPLN2 NM_021817.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2807874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAPLN2	NM_021817.3	c.220G>C	p.Glu74Gln	missense_variant	4/7	ENST00000255039.6
HAPLN2	XM_011509853.3	c.220G>C	p.Glu74Gln	missense_variant	4/7
HAPLN2	XM_017002020.2	c.220G>C	p.Glu74Gln	missense_variant	5/8
HAPLN2	XM_047427123.1	c.353G>C	p.Gly118Ala	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAPLN2	ENST00000255039.6	c.220G>C	p.Glu74Gln	missense_variant	4/7	1	NM_021817.3	P1
HAPLN2	ENST00000456112.1	c.220G>C	p.Glu74Gln	missense_variant	4/5	5
HAPLN2	ENST00000482204.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.093
Sift	Benign	0.34	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.96	D;.
Vest4		0.20
MutPred		0.34		Loss of ubiquitination at K72 (P = 0.0451);Loss of ubiquitination at K72 (P = 0.0451);
MVP		0.57
MPC		1.8
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.16
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156593733;