rs7860079

Variant names:

• chr9-2106237-G-C
• rs7860079
• NM_003070.5:c.3292+2068G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003070.5(SMARCA2):​c.3292+2068G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,268 control chromosomes in the GnomAD database, including 56,325 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (56325 hom., cov: 33)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability-sparse hair-brachydactyly syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCA2	NM_003070.5	c.3292+2068G>C		intron_variant	Intron 23 of 33	ENST00000349721.8	NP_003061.3
SMARCA2	NM_001289396.2	c.3292+2068G>C		intron_variant	Intron 23 of 33		NP_001276325.1
SMARCA2	NM_139045.4	c.3292+2068G>C		intron_variant	Intron 23 of 32		NP_620614.2
SMARCA2	NM_001289397.2	c.3118+2068G>C		intron_variant	Intron 23 of 32		NP_001276326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCA2	ENST00000349721.8	c.3292+2068G>C		intron_variant	Intron 23 of 33	5	NM_003070.5	ENSP00000265773.5

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130374 AN: 152150 Hom.: 56280 Cov.: 33

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.850

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.857 AC: 130474 AN: 152268 Hom.: 56325 Cov.: 33 AF XY: 0.859 AC XY: 63932 AN XY: 74446

African (AFR) AF: 0.964 AC: 40071 AN: 41570

American (AMR) AF: 0.836 AC: 12784 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2966 AN: 3472

East Asian (EAS) AF: 0.825 AC: 4276 AN: 5184

South Asian (SAS) AF: 0.830 AC: 3999 AN: 4818

European-Finnish (FIN) AF: 0.844 AC: 8955 AN: 10606

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54578 AN: 68012

Other (OTH) AF: 0.845 AC: 1787 AN: 2114

Alfa AF: 0.840 Hom.: 6799

Bravo AF: 0.861

Asia WGS AF: 0.818 AC: 2843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.7
DANN	Benign	0.77
PhyloP100		0.098
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7860079; hg19: chr9-2106237;