rs1555580263

Positions:

• chr17-63837200-G-GAGGTAGAACCTTATCTGCCATCTTC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001098426.2(SMARCD2):​c.438_439insGAAGATGGCAGATAAGGTTCTACCT​(p.Gln147GlufsTer5) variant causes a stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMARCD2 NM_001098426.2 stop_gained, frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 0.570

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-63837200-G-GAGGTAGAACCTTATCTGCCATCTTC is Pathogenic according to our data. Variant chr17-63837200-G-GAGGTAGAACCTTATCTGCCATCTTC is described in ClinVar as [Pathogenic]. Clinvar id is 369730.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCD2	NM_001098426.2	c.438_439insGAAGATGGCAGATAAGGTTCTACCT	p.Gln147GlufsTer5	stop_gained, frameshift_variant	3/13	ENST00000448276.7	NP_001091896.1
SMARCD2	NM_001330439.1	c.213_214insGAAGATGGCAGATAAGGTTCTACCT	p.Gln72GlufsTer5	stop_gained, frameshift_variant	3/13		NP_001317368.1
SMARCD2	NM_001330440.2	c.294_295insGAAGATGGCAGATAAGGTTCTACCT	p.Gln99GlufsTer5	stop_gained, frameshift_variant	3/13		NP_001317369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMARCD2	ENST00000448276.7	c.438_439insGAAGATGGCAGATAAGGTTCTACCT	p.Gln147GlufsTer5	stop_gained, frameshift_variant	3/13	1	NM_001098426.2	ENSP00000392617	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Specific granule deficiency 1;C5447331:Autosomal recessive severe congenital neutropenia Pathogenic:1

Pathogenic, no assertion criteria provided

in vitro;in vivo;research

Hauner Childrens Hospital, Department of Pediatrics, Dr. von Hauner Children's Hospital; Ludwig Maximilians University

Jan 01, 2016

- -

Specific granule deficiency 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555580263; hg19: chr17-61914560;