17-63840722-A-G

Variant names:

• chr17-63840722-A-G
• rs2727280
• NM_001098426.2:c.216+1737T>C

Variant summary

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

The NM_001098426.2(SMARCD2):​c.216+1737T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,096 control chromosomes in the GnomAD database, including 7,006 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 0.27 (7006 hom., cov: 32)
• Consequence: SMARCD2 NM_001098426.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 13 publications found

Genes affected

SMARCD2 (HGNC:11107): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, 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 has sequence similarity to the yeast Swp73 protein. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SMARCD2 Gene-Disease associations (from GenCC):

• specific granule deficiency 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• specific granule deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098426.2. 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
	SMARCD2	NM_001098426.2	MANE Select	c.216+1737T>C		intron	N/A	NP_001091896.1
	SMARCD2	NM_001330439.1		c.-10+1659T>C		intron	N/A	NP_001317368.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCD2	ENST00000448276.7	TSL:1 MANE Select	c.216+1737T>C		intron	N/A	ENSP00000392617.2
	SMARCD2	ENST00000225742.13	TSL:1	c.-10+1659T>C		intron	N/A	ENSP00000225742.9
	SMARCD2	ENST00000698022.1		c.33+1737T>C		intron	N/A	ENSP00000513504.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40744 AN: 151976 Hom.: 6992 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.268 AC: 40767 AN: 152096 Hom.: 7006 Cov.: 32 AF XY: 0.280 AC XY: 20849 AN XY: 74370

African (AFR) AF: 0.0721 AC: 2994 AN: 41526

American (AMR) AF: 0.340 AC: 5197 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 831 AN: 3466

East Asian (EAS) AF: 0.525 AC: 2712 AN: 5168

South Asian (SAS) AF: 0.551 AC: 2661 AN: 4830

European-Finnish (FIN) AF: 0.435 AC: 4598 AN: 10564

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20976 AN: 67948

Other (OTH) AF: 0.261 AC: 551 AN: 2110

Alfa AF: 0.246 Hom.: 2486

Bravo AF: 0.248

Asia WGS AF: 0.508 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.78
PhyloP100		0.15
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: rs2727280; hg19: chr17-61918082;