Variant 1-232425774-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020808.5(SIPA1L2):c.4445C>T(p.Ser1482Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00742 in 1,613,990 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 46 hom. )

Consequence

SIPA1L2
NM_020808.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.48

Variant links:

Genes affected

SIPA1L2 (HGNC:23800): (signal induced proliferation associated 1 like 2) This gene encodes a member of the signal-induced proliferation-associated 1 like family. Members of this family contain a GTPase activating domain, a PDZ domain and a C-terminal coiled-coil domain with a leucine zipper. A similar protein in rat acts as a GTPases for the small GTPase Rap. [provided by RefSeq, Sep 2015]

SIPA1L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009830773).

BP6

Variant 1-232425774-G-A is Benign according to our data. Variant chr1-232425774-G-A is described in ClinVar as [Benign]. Clinvar id is 718930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIPA1L2	NM_020808.5 linkuse as main transcript	c.4445C>T	p.Ser1482Leu	missense_variant	18/23	ENST00000674635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIPA1L2	ENST00000674635.1 linkuse as main transcript	c.4445C>T	p.Ser1482Leu	missense_variant	18/23		NM_020808.5	A1	Q9P2F8-1

Frequencies

GnomAD3 genomes

AF:

0.00493

AC:

750

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00833

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00557

AC:

1388

AN:

249064

Hom.:

AF XY:

0.00547

AC XY:

739

AN XY:

135126

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00826

Gnomad NFE exome

AF:

0.00918

Gnomad OTH exome

AF:

0.00544

GnomAD4 exome

AF:

0.00768

AC:

11228

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

5401

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.00914

Gnomad4 NFE exome

AF:

0.00907

Gnomad4 OTH exome

AF:

0.00556

GnomAD4 genome

AF:

0.00492

AC:

750

AN:

152316

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

360

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00622

Gnomad4 NFE

AF:

0.00833

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00686

Hom.:

Bravo

AF:

0.00430

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00233

AC:

ESP6500EA

AF:

0.00824

AC:

ExAC

AF:

0.00618

AC:

749

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00709

EpiControl

AF:

0.00830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 28, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T;.

Eigen

Benign

0.031

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.0098

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

M;M;.

MutationTaster

Benign

0.80

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.096

Sift

Uncertain

0.010

D;D;D

Sift4G

Benign

0.062

T;T;D

Polyphen

0.33

B;B;B

Vest4

0.65

MVP

0.093

MPC

0.20

ClinPred

0.028

GERP RS

4.8

Varity_R

0.19

gMVP

0.44

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over