Genetic Variant SMARCC2:c.2185+71A>T (chr12-56171608-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001330288.2(SMARCC2):c.2185+71A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,360,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SMARCC2
NM_001330288.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0700

Publications

21 publications found

Variant links:

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)

SMARCC2 links:

ENSG00000258199 (HGNC:):

ENSG00000258199 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMARCC2	NM_001330288.2	MANE Select	c.2185+71A>T	intron	N/A	NP_001317217.1
SMARCC2	NM_003075.5		c.2092+71A>T	intron	N/A	NP_003066.2
SMARCC2	NM_001130420.3		c.2185+71A>T	intron	N/A	NP_001123892.1

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.35e-7

AC:

AN:

1360572

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

668920

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30260

American (AMR)

AF:

0.00

AC:

AN:

31312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20260

East Asian (EAS)

AF:

0.00

AC:

AN:

38964

South Asian (SAS)

AF:

0.00

AC:

AN:

71112

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4102

European-Non Finnish (NFE)

AF:

9.44e-7

AC:

AN:

1059278

Other (OTH)

AF:

0.00

AC:

AN:

56038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.6

(source)

DANN

Benign

0.73

PhyloP100

0.070

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over