Variant 10-126039436-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001288973.2(ADAM12):c.2105-7G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00365 in 1,613,852 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 61 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 50 hom. )

Consequence

ADAM12
NM_001288973.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001435

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.432

Variant links:

Genes affected

ADAM12 (HGNC:190): (ADAM metallopeptidase domain 12) This gene encodes a member of a family of proteins that are structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. Expression of this gene has been used as a maternal serum marker for pre-natal development. Alternative splicing results in multiple transcript variants encoding different isoforms. Shorter isoforms are secreted, while longer isoforms are membrane-bound form. [provided by RefSeq, Jan 2014]

ADAM12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 10-126039436-C-G is Benign according to our data. Variant chr10-126039436-C-G is described in ClinVar as [Benign]. Clinvar id is 789034.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ADAM12	NM_001288973.2 linkuse as main transcript	c.2105-7G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000448723.2
ADAM12	NM_003474.6 linkuse as main transcript	c.2114-7G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ADAM12	XM_017016706.2 linkuse as main transcript	c.947-7G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ADAM12	XM_024448210.1 linkuse as main transcript	c.776-7G>C	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM12	ENST00000448723.2 linkuse as main transcript	c.2105-7G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001288973.2	A2
ADAM12	ENST00000368679.8 linkuse as main transcript	c.2114-7G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P2	O43184-1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2392

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0526

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00597

Gnomad SAS

AF:

0.00953

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00562

AC:

1412

AN:

251394

Hom.:

AF XY:

0.00484

AC XY:

657

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00495

Gnomad SAS exome

AF:

0.00869

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00239

AC:

3495

AN:

1461618

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

1766

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.0539

Gnomad4 AMR exome

AF:

0.00288

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00834

Gnomad4 SAS exome

AF:

0.00879

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.00441

GnomAD4 genome

AF:

0.0157

AC:

2395

AN:

152234

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1126

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0525

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00598

Gnomad4 SAS

AF:

0.00954

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.0182

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.5

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0020

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over