2-233841076-T-G

Variant names:

• chr2-233841076-T-G
• rs3771333
• NM_018410.5:c.1704A>C

Variant summary

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

The NM_018410.5(HJURP):​c.1704A>C​(p.Glu568Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,614,212 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (69 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (215 hom.)
• Consequence: HJURP NM_018410.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 19 publications found

Genes affected

HJURP (HGNC:25444): (Holliday junction recognition protein) Enables histone binding activity and identical protein binding activity. Involved in several processes, including CENP-A containing chromatin assembly; regulation of DNA binding activity; and regulation of protein-containing complex assembly. Located in kinetochore; mitochondrion; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016310215).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HJURP	NM_018410.5	c.1704A>C	p.Glu568Asp	missense_variant	Exon 8 of 9	ENST00000411486.7	NP_060880.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HJURP	ENST00000411486.7	c.1704A>C	p.Glu568Asp	missense_variant	Exon 8 of 9	1	NM_018410.5	ENSP00000414109.1
HJURP	ENST00000432087.5	c.1542A>C	p.Glu514Asp	missense_variant	Exon 6 of 7	2		ENSP00000407208.1
HJURP	ENST00000441687.5	c.1449A>C	p.Glu483Asp	missense_variant	Exon 5 of 6	2		ENSP00000401944.1
HJURP	ENST00000414924.5	c.1449A>C	p.Glu483Asp	missense_variant	Exon 5 of 5	4		ENSP00000393253.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2198 AN: 152206 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.0350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.0122 AC: 3078 AN: 251484 AF XY: 0.0109

Gnomad AFR exome AF: 0.0366

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00458 AC: 6696 AN: 1461888 Hom.: 215 Cov.: 34 AF XY: 0.00450 AC XY: 3276 AN XY: 727246

African (AFR) AF: 0.0383 AC: 1282 AN: 33480

American (AMR) AF: 0.00217 AC: 97 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000995 AC: 26 AN: 26136

East Asian (EAS) AF: 0.0885 AC: 3512 AN: 39696

South Asian (SAS) AF: 0.00980 AC: 845 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.000284 AC: 316 AN: 1112010

Other (OTH) AF: 0.0101 AC: 608 AN: 60396

GnomAD4 genome AF: 0.0145 AC: 2208 AN: 152324 Hom.: 69 Cov.: 32 AF XY: 0.0146 AC XY: 1091 AN XY: 74496

African (AFR) AF: 0.0351 AC: 1458 AN: 41564

American (AMR) AF: 0.00431 AC: 66 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.105 AC: 542 AN: 5184

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68034

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.00692 Hom.: 81

Bravo AF: 0.0170

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0352 AC: 155

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0127 AC: 1547

Asia WGS AF: 0.0680 AC: 238 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.099
DANN	Benign	0.95
DEOGEN2	Benign	0.0036	.;.;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.34	T;T;T;T
MetaRNN	Benign	0.0016	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;.;L;.
PhyloP100		-2.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.087
Sift	Benign	0.34	T;T;T;T
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.0090	B;B;B;.
Vest4		0.029
MutPred		0.050		.;.;Loss of methylation at K567 (P = 0.0786);.;
MPC		0.067
ClinPred		0.011	T
GERP RS		-8.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.030
gMVP		0.025
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: rs3771333; hg19: chr2-234749722; COSMIC: COSV64979185; COSMIC: COSV64979185;