Genetic Variant GSDMD:c.410+18_410+32dupAGGGCAGGGCAGGGC (chr8-143559981-G-GAGGGCAGGGCAGGGC) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_024736.7(GSDMD):c.410+18_410+32dupAGGGCAGGGCAGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 100 hom., cov: 0)

Exomes 𝑓: 0.032 ( 1031 hom. )

Failed GnomAD Quality Control

Consequence

GSDMD
NM_024736.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0313 (4754/152096) while in subpopulation NFE AF= 0.0354 (2408/67960). AF 95% confidence interval is 0.0343. There are 100 homozygotes in gnomad4. There are 2395 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMD	NM_024736.7 link	c.410+18_410+32dupAGGGCAGGGCAGGGC		intron_variant	Intron 3 of 10	ENST00000262580.9	NP_079012.3	P57764
GSDMD	NM_001166237.1 link	c.410+18_410+32dupAGGGCAGGGCAGGGC		intron_variant	Intron 6 of 13		NP_001159709.1	P57764

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMD	ENST00000262580.9 link	c.410+18_410+32dupAGGGCAGGGCAGGGC		intron_variant	Intron 3 of 10	1	NM_024736.7	ENSP00000262580.4		P57764

Frequencies

GnomAD3 genomes

AF:

0.0313

AC:

4752

AN:

151978

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0245

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00694

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0502

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0354

Gnomad OTH

AF:

0.0350

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0323

AC:

46376

AN:

1436268

Hom.:

1031

Cov.:

AF XY:

0.0322

AC XY:

23061

AN XY:

715348

show subpopulations

Gnomad4 AFR exome

AF:

0.0229

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0447

Gnomad4 EAS exome

AF:

0.00492

Gnomad4 SAS exome

AF:

0.0265

Gnomad4 FIN exome

AF:

0.0460

Gnomad4 NFE exome

AF:

0.0333

Gnomad4 OTH exome

AF:

0.0332

GnomAD4 genome

AF:

0.0313

AC:

4754

AN:

152096

Hom.:

100

Cov.:

AF XY:

0.0322

AC XY:

2395

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0246

Gnomad4 AMR

AF:

0.0269

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.00657

Gnomad4 SAS

AF:

0.0226

Gnomad4 FIN

AF:

0.0502

Gnomad4 NFE

AF:

0.0354

Gnomad4 OTH

AF:

0.0351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

8-143559981-GAGGGCAGGGC-GAGGGCAGGGCAGGGCAGGGCAGGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over