Genetic Variant KDM1A:p.Ala10_Ala18del (chr1-23019614-GGCGGCAGCCGCGGCGGCGGCGGCTGCA-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3BP6_Very_StrongBS2

The NM_001009999.3(KDM1A):c.27_53delCGCGGCGGCGGCGGCTGCAGCGGCAGC(p.Ala10_Ala18del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000365 in 1,426,404 control chromosomes in the GnomAD database, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00081 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

KDM1A
NM_001009999.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.52

Publications

0 publications found

Variant links:

Genes affected

KDM1A (HGNC:29079): (lysine demethylase 1A) This gene encodes a nuclear protein containing a SWIRM domain, a FAD-binding motif, and an amine oxidase domain. This protein is a component of several histone deacetylase complexes, though it silences genes by functioning as a histone demethylase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

KDM1A Gene-Disease associations (from GenCC):

palatal anomalies-widely spaced teeth-facial dysmorphism-developmental delay syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

KDM1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001009999.3

BP6

Variant 1-23019614-GGCGGCAGCCGCGGCGGCGGCGGCTGCA-G is Benign according to our data. Variant chr1-23019614-GGCGGCAGCCGCGGCGGCGGCGGCTGCA-G is described in ClinVar as Benign. ClinVar VariationId is 1970962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 124 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM1A	NM_001009999.3 link	c.27_53delCGCGGCGGCGGCGGCTGCAGCGGCAGC	p.Ala10_Ala18del	disruptive_inframe_deletion	Exon 1 of 21	ENST00000400181.9	NP_001009999.1	O60341-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM1A	ENST00000400181.9 link	c.27_53delCGCGGCGGCGGCGGCTGCAGCGGCAGC	p.Ala10_Ala18del	disruptive_inframe_deletion	Exon 1 of 21	1	NM_001009999.3	ENSP00000383042.5		O60341-2

Frequencies

GnomAD3 genomes

AF:

0.000809

AC:

123

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00105

AC:

AN:

72596

AF XY:

0.000733

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00738

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000137

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.000311

AC:

396

AN:

1274206

Hom.:

AF XY:

0.000303

AC XY:

190

AN XY:

627324

show subpopulations

African (AFR)

AF:

0.000195

AC:

AN:

25644

American (AMR)

AF:

0.00855

AC:

161

AN:

18838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19724

East Asian (EAS)

AF:

0.00

AC:

AN:

30004

South Asian (SAS)

AF:

0.0000492

AC:

AN:

61018

European-Finnish (FIN)

AF:

0.0000318

AC:

AN:

31442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3544

European-Non Finnish (NFE)

AF:

0.000195

AC:

201

AN:

1031834

Other (OTH)

AF:

0.000479

AC:

AN:

52158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000815

AC:

124

AN:

152198

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41554

American (AMR)

AF:

0.00628

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67972

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.000712

Hom.:

Bravo

AF:

0.00139

Asia WGS

AF:

0.000290

AC:

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KDM1A: BS1, BS2 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.5

Mutation Taster

=199/1

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over