chr8-143559981-G-GAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC

Position:

• chr8-143559981-G-GAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024736.7(GSDMD):​c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,588,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: GSDMD NM_024736.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

Genes affected

GSDMD (HGNC:25697): (gasdermin D) Gasdermin D is a member of the gasdermin family. Members of this family appear to play a role in regulation of epithelial proliferation. Gasdermin D has been suggested to act as a tumor suppressor. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

GSDMD (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMD	NM_024736.7	c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC		intron_variant		ENST00000262580.9	NP_079012.3
GSDMD	NM_001166237.1	c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC		intron_variant			NP_001159709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMD	ENST00000262580.9	c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC		intron_variant		1	NM_024736.7	ENSP00000262580.4

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 152000 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.0000195 AC: 28 AN: 1436510 Hom.: 0 Cov.: 35 AF XY: 0.0000294 AC XY: 21 AN XY: 715474

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000106

Gnomad4 FIN exome AF: 0.0000386

Gnomad4 NFE exome AF: 0.0000110

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 152000 Hom.: 0 Cov.: 0 AF XY: 0.0000404 AC XY: 3 AN XY: 74236

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000479

ClinVar

Not reported in ClinVar

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: rs59118283; hg19: chr8-144642151;