12-56171608-T-G

Variant names:

• chr12-56171608-T-G
• rs7311008
• NM_001330288.2:c.2185+71A>C

Variant summary

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

The NM_001330288.2(SMARCC2):​c.2185+71A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 1,512,318 control chromosomes in the GnomAD database, including 602,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (48591 hom., cov: 31)
  • Exomes 𝑓: 0.90 (554290 hom.)
• Consequence: SMARCC2 NM_001330288.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0700
• Publications: 21 publications found

Genes affected

SMARCC2 (HGNC:11105): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 2) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which 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 and contains a predicted leucine zipper motif typical of many transcription factors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SMARCC2 Gene-Disease associations (from GenCC):

• Coffin-Siris syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Coffin-Siris syndrome 8

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

ENSG00000258199 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-56171608-T-G is Benign according to our data. Variant chr12-56171608-T-G is described in ClinVar as Benign. ClinVar VariationId is 1286375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330288.2. 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
	SMARCC2	NM_001330288.2	MANE Select	c.2185+71A>C		intron	N/A	NP_001317217.1
	SMARCC2	NM_003075.5		c.2092+71A>C		intron	N/A	NP_003066.2
	SMARCC2	NM_001130420.3		c.2185+71A>C		intron	N/A	NP_001123892.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCC2	ENST00000550164.6	TSL:5 MANE Select	c.2185+71A>C		intron	N/A	ENSP00000449396.1
	SMARCC2	ENST00000267064.8	TSL:1	c.2092+71A>C		intron	N/A	ENSP00000267064.4
	SMARCC2	ENST00000394023.7	TSL:1	c.2185+71A>C		intron	N/A	ENSP00000377591.3

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115555 AN: 151974 Hom.: 48593 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.876

Gnomad ASJ AF: 0.880

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.831

GnomAD4 exome AF: 0.898 AC: 1221971 AN: 1360226 Hom.: 554290 Cov.: 25 AF XY: 0.901 AC XY: 602370 AN XY: 668774

African (AFR) AF: 0.342 AC: 10347 AN: 30252

American (AMR) AF: 0.921 AC: 28833 AN: 31306

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 17863 AN: 20260

East Asian (EAS) AF: 0.982 AC: 38281 AN: 38964

South Asian (SAS) AF: 0.925 AC: 65756 AN: 71102

European-Finnish (FIN) AF: 0.916 AC: 45086 AN: 49242

Middle Eastern (MID) AF: 0.882 AC: 3613 AN: 4098

European-Non Finnish (NFE) AF: 0.909 AC: 962969 AN: 1058974

Other (OTH) AF: 0.879 AC: 49223 AN: 56028

GnomAD4 genome AF: 0.760 AC: 115571 AN: 152092 Hom.: 48591 Cov.: 31 AF XY: 0.766 AC XY: 56924 AN XY: 74356

African (AFR) AF: 0.362 AC: 14979 AN: 41432

American (AMR) AF: 0.876 AC: 13386 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 3052 AN: 3470

East Asian (EAS) AF: 0.979 AC: 5067 AN: 5174

South Asian (SAS) AF: 0.925 AC: 4456 AN: 4816

European-Finnish (FIN) AF: 0.917 AC: 9725 AN: 10604

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62093 AN: 67998

Other (OTH) AF: 0.829 AC: 1746 AN: 2106

Alfa AF: 0.879 Hom.: 118597

Bravo AF: 0.739

Asia WGS AF: 0.903 AC: 3140 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.66
PhyloP100		0.070
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=22/78	disease causing

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: rs7311008; hg19: chr12-56565392;