NM_018097.3:c.593C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018097.3(HAUS2):​c.593C>T​(p.Ser198Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,584,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

HAUS2
NM_018097.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82
Variant links:
Genes affected
HAUS2 (HGNC:25530): (HAUS augmin like complex subunit 2) The protein encoded by this gene is a subunit of the augmin complex. The augmin complex plays a role in microtubule attachment to the kinetochore and central spindle formation. [provided by RefSeq, Apr 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08290169).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HAUS2NM_018097.3 linkc.593C>T p.Ser198Leu missense_variant Exon 6 of 6 ENST00000260372.8 NP_060567.1 Q9NVX0-1A0A024R9P0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HAUS2ENST00000260372.8 linkc.593C>T p.Ser198Leu missense_variant Exon 6 of 6 1 NM_018097.3 ENSP00000260372.3 Q9NVX0-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251294
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000126
AC:
18
AN:
1432456
Hom.:
0
Cov.:
25
AF XY:
0.0000154
AC XY:
11
AN XY:
714386
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000467
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000645
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.593C>T (p.S198L) alteration is located in exon 6 (coding exon 6) of the HAUS2 gene. This alteration results from a C to T substitution at nucleotide position 593, causing the serine (S) at amino acid position 198 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.13
T;.
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.083
T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-2.4
N;D
REVEL
Benign
0.29
Sift
Uncertain
0.018
D;D
Sift4G
Uncertain
0.026
D;D
Polyphen
0.92
P;B
Vest4
0.31
MVP
0.39
MPC
0.14
ClinPred
0.16
T
GERP RS
5.1
Varity_R
0.074
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs189692778; hg19: chr15-42858899; COSMIC: COSV53000904; COSMIC: COSV53000904; API