16-89279750-G-C

Variant names:

• chr16-89279750-G-C
• rs778726288
• NM_013275.6:c.6792C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_013275.6(ANKRD11):​c.6792C>G​(p.Pro2264Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,842 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. P2264P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ANKRD11 NM_013275.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15
• Publications: 0 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

ACMG classification

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=-0.88).
• BP7: Synonymous conserved (PhyloP=-3.14 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	NM_013275.6	MANE Select	c.6792C>G	p.Pro2264Pro	synonymous	Exon 9 of 13	NP_037407.4
	ANKRD11	NM_001256182.2		c.6792C>G	p.Pro2264Pro	synonymous	Exon 10 of 14	NP_001243111.1
	ANKRD11	NM_001256183.2		c.6792C>G	p.Pro2264Pro	synonymous	Exon 9 of 13	NP_001243112.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD11	ENST00000301030.10	TSL:5 MANE Select	c.6792C>G	p.Pro2264Pro	synonymous	Exon 9 of 13	ENSP00000301030.4
	ANKRD11	ENST00000378330.7	TSL:1	c.6792C>G	p.Pro2264Pro	synonymous	Exon 10 of 14	ENSP00000367581.2
	ANKRD11	ENST00000642600.2		c.6792C>G	p.Pro2264Pro	synonymous	Exon 9 of 13	ENSP00000495226.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1371842 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 675464

African (AFR) AF: 0.00 AC: 0 AN: 31360

American (AMR) AF: 0.00 AC: 0 AN: 35144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24052

East Asian (EAS) AF: 0.00 AC: 0 AN: 35754

South Asian (SAS) AF: 0.00 AC: 0 AN: 78500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4814

European-Non Finnish (NFE) AF: 9.34e-7 AC: 1 AN: 1071016

Other (OTH) AF: 0.00 AC: 0 AN: 57138

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.030
DANN	Benign	0.47
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3

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

Other links and lift over

dbSNP: rs778726288; hg19: chr16-89346158;