NM_018097.3:c.593C>A

Variant names:

• chr15-42566701-C-A
• rs189692778
• NM_018097.3:c.593C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018097.3(HAUS2):​c.593C>A​(p.Ser198*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: HAUS2 NM_018097.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018097.3. 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
	HAUS2	NM_018097.3	MANE Select	c.593C>A	p.Ser198*	stop_gained	Exon 6 of 6	NP_060567.1	Q9NVX0-1
	HAUS2	NM_001130447.2		c.500C>A	p.Ser167*	stop_gained	Exon 5 of 5	NP_001123919.1	Q9NVX0-3
	HAUS2	NM_001323631.2		c.311C>A	p.Ser104*	stop_gained	Exon 7 of 7	NP_001310560.1	Q9NVX0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAUS2	ENST00000260372.8	TSL:1 MANE Select	c.593C>A	p.Ser198*	stop_gained	Exon 6 of 6	ENSP00000260372.3	Q9NVX0-1
	HAUS2	ENST00000970518.1		c.590C>A	p.Ser197*	stop_gained	Exon 6 of 6	ENSP00000640577.1
	HAUS2	ENST00000935098.1		c.584C>A	p.Ser195*	stop_gained	Exon 6 of 6	ENSP00000605157.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432452 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 714386

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32744

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25942

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.00 AC: 0 AN: 85656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085390

Other (OTH) AF: 0.0000168 AC: 1 AN: 59438

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	36
DANN	Uncertain	0.98
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.88	D
PhyloP100		1.8
Vest4		0.075
GERP RS		5.1

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

Other links and lift over

dbSNP: rs189692778; hg19: chr15-42858899;