Genetic Variant GSDMD:c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGC (chr8-143559981-G-GAGGGCAGGGCAGGGCAGGGCAGGGC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_024736.7(GSDMD):c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 0)

Exomes 𝑓: 0.0019 ( 10 hom. )

Failed GnomAD Quality Control

Consequence

GSDMD
NM_024736.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024736.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMD	NM_024736.7	MANE Select	c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGC		intron	N/A	NP_079012.3
	GSDMD	NM_001166237.1		c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGC		intron	N/A	NP_001159709.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSDMD	ENST00000262580.9	TSL:1 MANE Select	c.410+32_410+33insAGGGCAGGGCAGGGCAGGGCAGGGC	intron	N/A	ENSP00000262580.4
GSDMD	ENST00000533063.5	TSL:1	c.554+32_554+33insAGGGCAGGGCAGGGCAGGGCAGGGC	intron	N/A	ENSP00000433958.1
GSDMD	ENST00000524846.5	TSL:2	n.1089_1090insAGGGCAGGGCAGGGCAGGGCAGGGC	non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

241

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000677

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00259

Gnomad OTH

AF:

0.000958

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00185

AC:

2662

AN:

1436472

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1274

AN XY:

715454

show subpopulations

African (AFR)

AF:

0.000305

AC:

AN:

32814

American (AMR)

AF:

0.000344

AC:

AN:

43602

Ashkenazi Jewish (ASJ)

AF:

0.000428

AC:

AN:

25716

East Asian (EAS)

AF:

0.0000761

AC:

AN:

39434

South Asian (SAS)

AF:

0.000189

AC:

AN:

84712

European-Finnish (FIN)

AF:

0.000193

AC:

AN:

51836

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00230

AC:

2519

AN:

1093194

Other (OTH)

AF:

0.00128

AC:

AN:

59464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

115

230

346

461

576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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

AF:

0.00158

AC:

241

AN:

152118

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

115

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.000675

AC:

AN:

41466

American (AMR)

AF:

0.000327

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00259

AC:

176

AN:

67974

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000955

Hom.:

183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

8-143559981-GAGGGCAGGGC-GAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over