chr9-2029053-C-T

Position:

chr9-2029053-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2

The NM_003070.5(SMARCA2):c.31C>T(p.Pro11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,555,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SMARCA2
NM_003070.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

SMARCA2 (HGNC:11098): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins and is highly similar to the brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, which contains a trinucleotide repeat (CAG) length polymorphism. [provided by RefSeq, Jan 2014]

SMARCA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SMARCA2. . Gene score misZ 5.054 (greater than the threshold 3.09). Trascript score misZ 4.663 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability-sparse hair-brachydactyly syndrome, Coffin-Siris syndrome 1.

BP4

Computational evidence support a benign effect (MetaRNN=0.016416967).

BP6

Variant 9-2029053-C-T is Benign according to our data. Variant chr9-2029053-C-T is described in ClinVar as [Benign]. Clinvar id is 2174807.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00019 (29/152376) while in subpopulation AFR AF= 0.000697 (29/41594). AF 95% confidence interval is 0.000498. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SMARCA2	NM_003070.5 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/34	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.1 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/34		NP_001276325.1
SMARCA2	NM_139045.4 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/33		NP_620614.2
SMARCA2	NM_001289397.2 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/33		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/34	5	NM_003070.5	ENSP00000265773	P2	P51531-1

Frequencies

GnomAD3 genomes

AF:

0.000190

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000699

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000498

AC:

AN:

160634

Hom.:

AF XY:

0.0000583

AC XY:

AN XY:

85784

show subpopulations

Gnomad AFR exome

AF:

0.000809

Gnomad AMR exome

AF:

0.0000395

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000271

AC:

AN:

1402874

Hom.:

Cov.:

AF XY:

0.0000260

AC XY:

AN XY:

692698

show subpopulations

Gnomad4 AFR exome

AF:

0.00101

Gnomad4 AMR exome

AF:

0.0000551

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000688

GnomAD4 genome

AF:

0.000190

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.00

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:

0.0000966

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.000686

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000517

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

.;.;T;T;T;T;T;.;T;T;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.082

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.94

.;D;.;.;.;D;D;D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.016

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.29

MutationAssessor

Benign

0.97

L;.;.;L;.;.;.;L;.;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.4

N;N;.;N;.;.;D;N;D;.;N

REVEL

Benign

0.28

Sift

Benign

0.53

T;T;.;T;.;.;T;T;T;.;T

Sift4G

Benign

0.16

T;T;.;T;.;.;T;T;T;.;T

Polyphen

0.019

B;.;.;B;.;.;.;B;.;.;B

Vest4

0.14

MVP

0.47

MPC

0.048

ClinPred

0.033

GERP RS

5.5

Varity_R

0.13

gMVP

0.24

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