rs770199415

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001272071.2(AP1S2):c.289-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,184,871 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 44 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.00010 ( 0 hom. 39 hem. )

Consequence

AP1S2
NM_001272071.2 splice_region, intron

Scores

Splicing: ADA: 0.00005072

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.606

Publications

0 publications found

Variant links:

Genes affected

AP1S2 (HGNC:560): (adaptor related protein complex 1 subunit sigma 2) Adaptor protein complex 1 is found at the cytoplasmic face of coated vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. This complex is a heterotetramer composed of two large, one medium, and one small adaptin subunit. The protein encoded by this gene serves as the small subunit of this complex and is a member of the adaptin protein family. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

AP1S2 Gene-Disease associations (from GenCC):

syndromic X-linked intellectual disability 5
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
X-linked syndromic intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
fried syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
autism spectrum disorder
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

AP1S2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant X-15845524-G-A is Benign according to our data. Variant chrX-15845524-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1S2	NM_001272071.2 link	c.289-8C>T		splice_region_variant, intron_variant	Intron 3 of 5	ENST00000672987.1	NP_001259000.1	A0A5F9ZHW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1S2	ENST00000672987.1 link	c.289-8C>T		splice_region_variant, intron_variant	Intron 3 of 5		NM_001272071.2	ENSP00000500695.1		A0A5F9ZHW1

Frequencies

GnomAD3 genomes

AF:

0.000168

AC:

AN:

107293

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000347

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000152

AC:

AN:

164646

AF XY:

0.0000513

show subpopulations

Gnomad AFR exome

AF:

0.0000836

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000648

Gnomad NFE exome

AF:

0.000294

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

110

AN:

1077578

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

351766

show subpopulations

African (AFR)

AF:

0.0000402

AC:

AN:

24862

American (AMR)

AF:

0.0000320

AC:

AN:

31232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18649

East Asian (EAS)

AF:

0.0000335

AC:

AN:

29838

South Asian (SAS)

AF:

0.00

AC:

AN:

49988

European-Finnish (FIN)

AF:

0.0000500

AC:

AN:

40008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3689

European-Non Finnish (NFE)

AF:

0.000123

AC:

103

AN:

834235

Other (OTH)

AF:

0.0000444

AC:

AN:

45077

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000168

AC:

AN:

107293

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

30795

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29412

American (AMR)

AF:

0.00

AC:

AN:

10047

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2593

East Asian (EAS)

AF:

0.00

AC:

AN:

3525

South Asian (SAS)

AF:

0.00

AC:

AN:

2545

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.000347

AC:

AN:

51809

Other (OTH)

AF:

0.00

AC:

AN:

1434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00123

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

AP1S2: BP4, BS2 -

not specified

Benign:1

Dec 16, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Sep 19, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

AP1S2-related disorder

Benign:1

Jun 06, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.9

(source)

DANN

Benign

0.53

PhyloP100

0.61

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000051

dbscSNV1_RF

Benign

0.0040

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over