Genetic Variant ANKRD11:p.Pro2028Pro (chr16-89280458-G-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_013275.6(ANKRD11):c.6084C>A(p.Pro2028Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P2028P) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKRD11
NM_013275.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.84

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

ANKRD11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP7

Synonymous conserved (PhyloP=-6.84 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ANKRD11	NM_013275.6 link	c.6084C>A	p.Pro2028Pro	synonymous_variant	Exon 9 of 13	ENST00000301030.10	NP_037407.4
ANKRD11	NM_001256182.2 link	c.6084C>A	p.Pro2028Pro	synonymous_variant	Exon 10 of 14		NP_001243111.1
ANKRD11	NM_001256183.2 link	c.6084C>A	p.Pro2028Pro	synonymous_variant	Exon 9 of 13		NP_001243112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10 link	c.6084C>A	p.Pro2028Pro	synonymous_variant	Exon 9 of 13	5	NM_013275.6	ENSP00000301030.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000460

AC:

AN:

217430

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:

0.0000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441956

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32832

American (AMR)

AF:

0.00

AC:

AN:

42808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25442

East Asian (EAS)

AF:

0.00

AC:

AN:

39112

South Asian (SAS)

AF:

0.00

AC:

AN:

85050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5394

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1101064

Other (OTH)

AF:

0.00

AC:

AN:

59204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.011

(source)

DANN

Benign

0.56

PhyloP100

-6.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over