Genetic Variant ANKRD11:p.Pro2645Pro (chr16-89268535-G-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_013275.6(ANKRD11):c.7935C>G(p.Pro2645Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,470,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ANKRD11
NM_013275.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0630

Publications

0 publications found

Variant links:

Genes affected

ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]

ANKRD11 Gene-Disease associations (from GenCC):

KBG syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Illumina, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
congenital heart defects, multiple types
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ANKRD11 links:

ENSG00000268218 (HGNC:):

ENSG00000268218 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 16-89268535-G-C is Benign according to our data. Variant chr16-89268535-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3648551.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.063 with no splicing effect.

BS2

High AC in GnomAdExome4 at 28 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013275.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD11	NM_013275.6	MANE Select	c.7935C>G	p.Pro2645Pro	synonymous	Exon 13 of 13	NP_037407.4
ANKRD11	NM_001256182.2		c.7935C>G	p.Pro2645Pro	synonymous	Exon 14 of 14	NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2		c.7935C>G	p.Pro2645Pro	synonymous	Exon 13 of 13	NP_001243112.1	Q6UB99

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.7935C>G	p.Pro2645Pro	synonymous	Exon 13 of 13	ENSP00000301030.4	Q6UB99
ANKRD11	ENST00000378330.7	TSL:1	c.7935C>G	p.Pro2645Pro	synonymous	Exon 14 of 14	ENSP00000367581.2	Q6UB99
ANKRD11	ENST00000642600.2		c.7935C>G	p.Pro2645Pro	synonymous	Exon 13 of 13	ENSP00000495226.1	Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149662

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000653

AC:

AN:

153158

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000175

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1320788

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

653366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30210

American (AMR)

AF:

0.00

AC:

AN:

35620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24702

East Asian (EAS)

AF:

0.00

AC:

AN:

35564

South Asian (SAS)

AF:

0.00

AC:

AN:

77888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4058

European-Non Finnish (NFE)

AF:

0.0000278

AC:

AN:

1008928

Other (OTH)

AF:

0.00

AC:

AN:

55244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149662

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72922

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40544

American (AMR)

AF:

0.00

AC:

AN:

14998

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5054

South Asian (SAS)

AF:

0.00

AC:

AN:

4612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

67422

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

KBG syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.063

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over