rs6818964

Variant names:

• chr4-73104747-C-G
• rs6818964
• NM_032217.5:c.4402-2200G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-73104747-C-G
• chr4-73104747-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032217.5(ANKRD17):​c.4402-2200G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.000014 (0 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ANKRD17 NM_032217.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 2 publications found

Genes affected

ANKRD17 (HGNC:23575): (ankyrin repeat domain 17) The protein encoded by this gene belongs to the family of ankyrin repeat-containing proteins, and contains two distinct arrays of ankyrin repeats in its amino-terminal region, one with 15 ankyrin repeats, and the other with 10 ankyrin repeats. It also contains a nuclear export signal, nuclear localization signal, and a cyclin-binding RXL motif. Localization of this protein to the nucleus has been shown experimentally, and interactions between this protein and cyclin-dependent kinase 2 have been observed. It has been suggested that this protein plays a role in both DNA replication and in both anti-viral and anti-bacterial innate immune pathways. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ANKRD17 Gene-Disease associations (from GenCC):

• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Chopra-Amiel-Gordon syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ENSG00000303699 (HGNC:58814):

LOC124900713 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032217.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD17	NM_032217.5	MANE Select	c.4402-2200G>C		intron	N/A	NP_115593.3
	ANKRD17	NM_015574.2		c.4399-2200G>C		intron	N/A	NP_056389.1	O75179-2
	ANKRD17	NM_001286771.3		c.4063-2200G>C		intron	N/A	NP_001273700.1	O75179-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD17	ENST00000358602.9	TSL:5 MANE Select	c.4402-2200G>C		intron	N/A	ENSP00000351416.4	O75179-1
	ANKRD17	ENST00000509867.6	TSL:1	c.4063-2200G>C		intron	N/A	ENSP00000427151.2	O75179-7
	ANKRD17	ENST00000558247.5	TSL:1	c.4051-2200G>C		intron	N/A	ENSP00000453434.1	H0YM23

Frequencies

GnomAD3 genomes AF: 0.0000143 AC: 2 AN: 140178 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000727

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: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000143 AC: 2 AN: 140178 Hom.: 0 Cov.: 31 AF XY: 0.0000148 AC XY: 1 AN XY: 67606

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000271 AC: 1 AN: 36950

American (AMR) AF: 0.0000727 AC: 1 AN: 13756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3392

East Asian (EAS) AF: 0.00 AC: 0 AN: 4652

South Asian (SAS) AF: 0.00 AC: 0 AN: 4356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65284

Other (OTH) AF: 0.00 AC: 0 AN: 1890

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 67

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.24
PhyloP100		-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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6818964;

hg19: chr4-73970464;