chr17-39212390-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

The NM_198993.5(STAC2):c.1138G>A(p.Val380Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000442 in 1,606,352 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

STAC2
NM_198993.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.18

Publications

1 publications found

Variant links:

Genes affected

STAC2 (HGNC:23990): (SH3 and cysteine rich domain 2) This gene encodes a protein containing an SH3 domain and a zinc finger domain. The encoded protein has been shown to regulate calcium channel inactivation in a human cell line. Reduced expression of this gene has been observed in human heart failure. [provided by RefSeq, May 2017]

STAC2 links:

ENSG00000309604 (HGNC:):

ENSG00000309604 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: -0.099891 (below the threshold of 3.09). Trascript score misZ: 0.30072 (below the threshold of 3.09).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAC2	NM_198993.5 link	c.1138G>A	p.Val380Met	missense_variant	Exon 11 of 11	ENST00000333461.6	NP_945344.1	Q6ZMT1-1D0IN09
STAC2	NM_001351360.2 link	c.712G>A	p.Val238Met	missense_variant	Exon 11 of 11		NP_001338289.1
STAC2	XM_017024580.2 link	c.1153G>A	p.Val385Met	missense_variant	Exon 11 of 11		XP_016880069.1
STAC2	XM_017024581.2 link	c.988G>A	p.Val330Met	missense_variant	Exon 9 of 9		XP_016880070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STAC2	ENST00000333461.6 link	c.1138G>A	p.Val380Met	missense_variant	Exon 11 of 11	1	NM_198993.5	ENSP00000327509.5	Q6ZMT1-1
STAC2	ENST00000584501.1 link	n.*489G>A		non_coding_transcript_exon_variant	Exon 11 of 11	1		ENSP00000463299.1	J3QKZ0
STAC2	ENST00000584501.1 link	n.*489G>A		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000463299.1	J3QKZ0
ENSG00000309604	ENST00000842273.1 link	n.*244C>T		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000469

AC:

AN:

234734

AF XY:

0.0000315

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000871

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000461

AC:

AN:

1454144

Hom.:

Cov.:

AF XY:

0.0000387

AC XY:

AN XY:

722630

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33358

American (AMR)

AF:

0.0000226

AC:

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25838

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.0000354

AC:

AN:

84818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000560

AC:

AN:

1107776

Other (OTH)

AF:

0.0000166

AC:

AN:

60102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 05, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1138G>A (p.V380M) alteration is located in exon 11 (coding exon 11) of the STAC2 gene. This alteration results from a G to A substitution at nucleotide position 1138, causing the valine (V) at amino acid position 380 to be replaced by a methionine (M). 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

Pathogenic

0.65

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.080

MetaRNN

Uncertain

0.62

MetaSVM

Uncertain

0.42

MutationAssessor

Uncertain

2.1

PhyloP100

6.2

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.97

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.59

MVP

0.83

MPC

0.35

ClinPred

0.29

GERP RS

4.6

Varity_R

0.52

gMVP

0.65

Mutation Taster

=55/45

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over