17-63833154-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001098426.2(SMARCD2):c.1457T>C(p.Ile486Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,608,504 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (11 hom.)
• Consequence: SMARCD2 NM_001098426.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.95

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022360384).
• BP6: Variant 17-63833154-A-G is Benign according to our data. Variant chr17-63833154-A-G is described in ClinVar as [Benign]. Clinvar id is 717041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00542 (826/152276) while in subpopulation AFR AF= 0.0193 (800/41554). AF 95% confidence interval is 0.0181. There are 7 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMARCD2	NM_001098426.2	c.1457T>C	p.Ile486Thr	missense_variant	12/13	ENST00000448276.7
SMARCD2	NM_001330440.2	c.1313T>C	p.Ile438Thr	missense_variant	12/13
SMARCD2	NM_001330439.1	c.1232T>C	p.Ile411Thr	missense_variant	12/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCD2	ENST00000448276.7	c.1457T>C	p.Ile486Thr	missense_variant	12/13	1	NM_001098426.2	P1

Frequencies

GnomAD3 genomes AF: 0.00532 AC: 810 AN: 152158 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00142 AC: 339 AN: 238614 Hom.: 3 AF XY: 0.00112 AC XY: 145 AN XY: 129320

Gnomad AFR exome AF: 0.0208

Gnomad AMR exome AF: 0.00109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.000342

GnomAD4 exome AF: 0.000567 AC: 825 AN: 1456228 Hom.: 11 Cov.: 33 AF XY: 0.000506 AC XY: 366 AN XY: 723924

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.00117

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000703

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00542 AC: 826 AN: 152276 Hom.: 7 Cov.: 32 AF XY: 0.00540 AC XY: 402 AN XY: 74462

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000866 Hom.: 2

Bravo AF: 0.00608

ESP6500AA AF: 0.0190 AC: 75

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.00188 AC: 227

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	15
Dann	Benign	0.82
DEOGEN2	Benign	0.0069	T;T;.;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.80	T;T;T;T
MetaRNN	Benign	0.0022	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.32	T;T;T;T
Polyphen		0.0010	B;B;B;.
Vest4		0.14
MVP		0.043
MPC		0.78
ClinPred		0.0058	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.049
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs1130111; hg19: chr17-61910514;