NM_003070.5:c.-5G>A

Variant names:

• chr9-2029018-G-A
• rs10964468
• NM_003070.5:c.-5G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003070.5(SMARCA2):​c.-5G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,547,988 control chromosomes in the GnomAD database, including 8,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1599 hom., cov: 33)
  • Exomes 𝑓: 0.094 (7123 hom.)
• Consequence: SMARCA2 NM_003070.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.00500
• Publications: 12 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: PanelApp Australia, Orphanet, G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• blepharophimosis-impaired intellectual development syndrome

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 9-2029018-G-A is Benign according to our data. Variant chr9-2029018-G-A is described in ClinVar as Benign. ClinVar VariationId is 126341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003070.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA2	NM_003070.5	MANE Select	c.-5G>A		5_prime_UTR	Exon 2 of 34	NP_003061.3
	SMARCA2	NM_001289396.2		c.-5G>A		5_prime_UTR	Exon 2 of 34	NP_001276325.1	P51531-1
	SMARCA2	NM_139045.4		c.-5G>A		5_prime_UTR	Exon 2 of 33	NP_620614.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA2	ENST00000349721.8	TSL:5 MANE Select	c.-5G>A		5_prime_UTR	Exon 2 of 34	ENSP00000265773.5	P51531-1
	SMARCA2	ENST00000382203.5	TSL:1	c.-5G>A		5_prime_UTR	Exon 2 of 34	ENSP00000371638.1	P51531-1
	SMARCA2	ENST00000450198.6	TSL:1	c.-5G>A		5_prime_UTR	Exon 2 of 33	ENSP00000392081.2	F6VDE0

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19743 AN: 152192 Hom.: 1590 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0750

Gnomad FIN AF: 0.0578

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0842

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.115 AC: 17070 AN: 149066 AF XY: 0.108

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.0766

Gnomad EAS exome AF: 0.126

Gnomad FIN exome AF: 0.0511

Gnomad NFE exome AF: 0.0833

Gnomad OTH exome AF: 0.0969

GnomAD4 exome AF: 0.0940 AC: 131232 AN: 1395678 Hom.: 7123 Cov.: 33 AF XY: 0.0922 AC XY: 63467 AN XY: 688540

African (AFR) AF: 0.219 AC: 6859 AN: 31374

American (AMR) AF: 0.244 AC: 8469 AN: 34760

Ashkenazi Jewish (ASJ) AF: 0.0783 AC: 1962 AN: 25054

East Asian (EAS) AF: 0.141 AC: 5043 AN: 35758

South Asian (SAS) AF: 0.0716 AC: 5666 AN: 79114

European-Finnish (FIN) AF: 0.0522 AC: 2548 AN: 48852

Middle Eastern (MID) AF: 0.0612 AC: 273 AN: 4464

European-Non Finnish (NFE) AF: 0.0879 AC: 94804 AN: 1078504

Other (OTH) AF: 0.0970 AC: 5608 AN: 57798

GnomAD4 genome AF: 0.130 AC: 19787 AN: 152310 Hom.: 1599 Cov.: 33 AF XY: 0.129 AC XY: 9610 AN XY: 74470

African (AFR) AF: 0.216 AC: 8961 AN: 41562

American (AMR) AF: 0.195 AC: 2992 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3470

East Asian (EAS) AF: 0.114 AC: 592 AN: 5186

South Asian (SAS) AF: 0.0749 AC: 362 AN: 4834

European-Finnish (FIN) AF: 0.0578 AC: 613 AN: 10614

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0842 AC: 5727 AN: 68018

Other (OTH) AF: 0.112 AC: 237 AN: 2110

Alfa AF: 0.105 Hom.: 2305

Bravo AF: 0.148

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Nicolaides-Baraitser syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.6
DANN	Benign	0.93
PhyloP100		0.0050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	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: rs10964468; hg19: chr9-2029018; COSMIC: COSV100571671;