15-58599750-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001110.4(ADAM10):c.2026-27del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26170 hom., cov: 0)
  • Exomes 𝑓: 0.39 (38652 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAM10 NM_001110.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25

Genes affected

ADAM10 (HGNC:188): (ADAM metallopeptidase domain 10) Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-58599750-GA-G is Benign according to our data. Variant chr15-58599750-GA-G is described in ClinVar as [Benign]. Clinvar id is 1228846.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM10	NM_001110.4	c.2026-27del		intron_variant		ENST00000260408.8
ADAM10	NM_001320570.2	c.1933-27del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM10	ENST00000260408.8	c.2026-27del		intron_variant		1	NM_001110.4	P1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 84239 AN: 144452 Hom.: 26136 Cov.: 0

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.544

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.389 AC: 494765 AN: 1273488 Hom.: 38652 Cov.: 0 AF XY: 0.389 AC XY: 247994 AN XY: 636774

Gnomad4 AFR exome AF: 0.578

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.360

Gnomad4 EAS exome AF: 0.644

Gnomad4 SAS exome AF: 0.454

Gnomad4 FIN exome AF: 0.454

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.404

GnomAD4 genome AF: 0.583 AC: 84322 AN: 144540 Hom.: 26170 Cov.: 0 AF XY: 0.593 AC XY: 41590 AN XY: 70188

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.545

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs35772938; hg19: chr15-58891949;