rs2353033

Variant names:

• chr16-89319153-C-T
• rs2353033
• NM_013275.6:c.-59-2075G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013275.6(ANKRD11):​c.-59-2075G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,150 control chromosomes in the GnomAD database, including 20,631 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20631 hom., cov: 34)
• Consequence: ANKRD11 NM_013275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• Publications: 24 publications found

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

ENSG00000288715 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD11	NM_013275.6	c.-59-2075G>A		intron_variant	Intron 2 of 12	ENST00000301030.10	NP_037407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10	c.-59-2075G>A		intron_variant	Intron 2 of 12	5	NM_013275.6	ENSP00000301030.4
ENSG00000288715	ENST00000711617.1	c.10-2078G>A		intron_variant	Intron 1 of 1			ENSP00000518812.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78238 AN: 152032 Hom.: 20622 Cov.: 34

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.514 AC: 78268 AN: 152150 Hom.: 20631 Cov.: 34 AF XY: 0.509 AC XY: 37889 AN XY: 74382

African (AFR) AF: 0.440 AC: 18238 AN: 41492

American (AMR) AF: 0.535 AC: 8188 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3472

East Asian (EAS) AF: 0.284 AC: 1469 AN: 5164

South Asian (SAS) AF: 0.483 AC: 2325 AN: 4816

European-Finnish (FIN) AF: 0.462 AC: 4890 AN: 10590

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38811 AN: 68004

Other (OTH) AF: 0.572 AC: 1206 AN: 2110

Alfa AF: 0.563 Hom.: 47051

Bravo AF: 0.516

Asia WGS AF: 0.380 AC: 1324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.74
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2353033; hg19: chr16-89385561;