9-2029126-C-T

Position:

chr9-2029126-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS1

The NM_003070.5(SMARCA2):c.104C>T(p.Pro35Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,609,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SMARCA2
NM_003070.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.01

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 -7 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). The gene has 93 curated pathogenic missense variants (we use a threshold of 10). The gene has 88 curated benign missense variants. GenCC has associacion of the gene with intellectual disability-sparse hair-brachydactyly syndrome, Coffin-Siris syndrome 1.

BP4

Computational evidence support a benign effect (MetaRNN=0.11590147).

BP6

Variant 9-2029126-C-T is Benign according to our data. Variant chr9-2029126-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2720233.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00000275 (4/1456982) while in subpopulation AFR AF= 0.00012 (4/33354). AF 95% confidence interval is 0.0000409. There are 0 homozygotes in gnomad4_exome. There are 1 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA2	NM_003070.5 link	c.104C>T	p.Pro35Leu	missense_variant	2/34	ENST00000349721.8	NP_003061.3	P51531-1Q8N9Q1Q56A76
SMARCA2	NM_001289396.2 link	c.104C>T	p.Pro35Leu	missense_variant	2/34		NP_001276325.1	P51531-1Q8N9Q1B4DSC8
SMARCA2	NM_139045.4 link	c.104C>T	p.Pro35Leu	missense_variant	2/33		NP_620614.2	P51531-2Q8N9Q1Q56A76
SMARCA2	NM_001289397.2 link	c.104C>T	p.Pro35Leu	missense_variant	2/33		NP_001276326.1	P51531F6VDE0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8 link	c.104C>T	p.Pro35Leu	missense_variant	2/34	5	NM_003070.5	ENSP00000265773.5		P51531-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00000823

AC:

AN:

242982

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131392

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.00

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:

0.00000275

AC:

AN:

1456982

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724272

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

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:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

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

Eigen

Benign

-0.11

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

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

M_CAP

Benign

0.022

MetaRNN

Benign

0.12

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

MetaSVM

Benign

-0.37

MutationAssessor

Benign

0.46

N;.;.;N;.;.;.;N;.;.;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.7

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

REVEL

Uncertain

0.33

Sift

Benign

0.056

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

Sift4G

Benign

0.082

T;T;.;T;.;.;D;T;D;.;T

Polyphen

0.0030

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

Vest4

0.29

MutPred

0.18

Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);Loss of glycosylation at P35 (P = 0.0357);

MVP

0.60

MPC

0.048

ClinPred

0.15

GERP RS

5.8

Varity_R

0.11

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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