rs2144624108

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001098426.2(SMARCD2):c.1585C>T(p.Arg529Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000212 in 1,417,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R529P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SMARCD2
NM_001098426.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.50

Publications

0 publications found

Variant links:

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

SMARCD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMARCD2	NM_001098426.2 link	c.1585C>T	p.Arg529Cys	missense_variant	Exon 13 of 13	ENST00000448276.7	NP_001091896.1	Q92925-1
SMARCD2	NM_001330440.2 link	c.1441C>T	p.Arg481Cys	missense_variant	Exon 13 of 13		NP_001317369.1	Q92925-3
SMARCD2	NM_001330439.1 link	c.1360C>T	p.Arg454Cys	missense_variant	Exon 13 of 13		NP_001317368.1	J3KMX2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMARCD2	ENST00000448276.7 link	c.1585C>T	p.Arg529Cys	missense_variant	Exon 13 of 13	1	NM_001098426.2	ENSP00000392617.2		Q92925-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1417770

Hom.:

Cov.:

AF XY:

0.00000428

AC XY:

AN XY:

701288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32186

American (AMR)

AF:

0.00

AC:

AN:

38562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25354

East Asian (EAS)

AF:

0.00

AC:

AN:

37052

South Asian (SAS)

AF:

0.00

AC:

AN:

80244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4108

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1090998

Other (OTH)

AF:

0.0000170

AC:

AN:

58728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1585C>T (p.R529C) alteration is located in exon 13 (coding exon 13) of the SMARCD2 gene. This alteration results from a C to T substitution at nucleotide position 1585, causing the arginine (R) at amino acid position 529 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.15

T;T;.;T

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.58

D;D;D;D

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.5

.;M;.;.

PhyloP100

5.5

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.9

.;D;D;.

REVEL

Pathogenic

0.68

Sift

Pathogenic

0.0

.;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.34

MutPred

0.76

.;Loss of disorder (P = 0.0028);.;.;

MVP

0.54

MPC

0.86

ClinPred

0.99

GERP RS

5.3

Varity_R

0.62

gMVP

0.62

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over