chr9-2076174-A-T

Variant names:

• chr9-2076174-A-T
• rs3763627
• NM_003070.5:c.1936-55A>T

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.1936-55A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 968,268 control chromosomes in the GnomAD database, including 5,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (800 hom., cov: 32)
  • Exomes 𝑓: 0.10 (5156 hom.)
• Consequence: SMARCA2 NM_003070.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.619
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-2076174-A-T is Benign according to our data. Variant chr9-2076174-A-T is described in ClinVar as Benign. ClinVar VariationId is 1270525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA2	NM_003070.5	MANE Select	c.1936-55A>T		intron	N/A	NP_003061.3
	SMARCA2	NM_001289396.2		c.1936-55A>T		intron	N/A	NP_001276325.1
	SMARCA2	NM_139045.4		c.1936-55A>T		intron	N/A	NP_620614.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA2	ENST00000349721.8	TSL:5 MANE Select	c.1936-55A>T		intron	N/A	ENSP00000265773.5
	SMARCA2	ENST00000382203.5	TSL:1	c.1936-55A>T		intron	N/A	ENSP00000371638.1
	SMARCA2	ENST00000450198.6	TSL:1	c.1936-55A>T		intron	N/A	ENSP00000392081.2

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14250 AN: 152078 Hom.: 795 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.103 AC: 83770 AN: 816072 Hom.: 5156 AF XY: 0.101 AC XY: 43498 AN XY: 431776

African (AFR) AF: 0.0591 AC: 1192 AN: 20166

American (AMR) AF: 0.179 AC: 7068 AN: 39550

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 1944 AN: 21092

East Asian (EAS) AF: 0.267 AC: 9807 AN: 36770

South Asian (SAS) AF: 0.0975 AC: 6806 AN: 69814

European-Finnish (FIN) AF: 0.105 AC: 5534 AN: 52688

Middle Eastern (MID) AF: 0.0323 AC: 143 AN: 4430

European-Non Finnish (NFE) AF: 0.0886 AC: 47198 AN: 532548

Other (OTH) AF: 0.105 AC: 4078 AN: 39014

GnomAD4 genome AF: 0.0938 AC: 14272 AN: 152196 Hom.: 800 Cov.: 32 AF XY: 0.0968 AC XY: 7206 AN XY: 74418

African (AFR) AF: 0.0581 AC: 2411 AN: 41532

American (AMR) AF: 0.142 AC: 2173 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3466

East Asian (EAS) AF: 0.276 AC: 1426 AN: 5160

South Asian (SAS) AF: 0.114 AC: 549 AN: 4824

European-Finnish (FIN) AF: 0.107 AC: 1136 AN: 10600

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0874 AC: 5942 AN: 67998

Other (OTH) AF: 0.109 AC: 231 AN: 2116

Alfa AF: 0.0289 Hom.: 24

Bravo AF: 0.0966

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.35
DANN	Benign	0.76
PhyloP100		-0.62
PromoterAI		-0.023	Neutral
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: rs3763627; hg19: chr9-2076174; COSMIC: COSV61813146; COSMIC: COSV61813146;