rs2306058

Variant names:

• chr4-73076961-C-A
• rs2306058
• NM_032217.5:c.7731G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-73076961-C-A
• chr4-73076961-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_032217.5(ANKRD17):​c.7731G>T​(p.Thr2577Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T2577T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD17 NM_032217.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• Publications: 0 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):

• Chopra-Amiel-Gordon syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP7: Synonymous conserved (PhyloP=0.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD17	NM_032217.5	c.7731G>T	p.Thr2577Thr	synonymous_variant	Exon 33 of 34	ENST00000358602.9	NP_115593.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD17	ENST00000358602.9	c.7731G>T	p.Thr2577Thr	synonymous_variant	Exon 33 of 34	5	NM_032217.5	ENSP00000351416.4
ANKRD17	ENST00000509867.6	c.7392G>T	p.Thr2464Thr	synonymous_variant	Exon 33 of 34	1		ENSP00000427151.2
ANKRD17	ENST00000558247.5	c.7380G>T	p.Thr2460Thr	synonymous_variant	Exon 33 of 34	1		ENSP00000453434.1
ANKRD17	ENST00000330838.10	c.6978G>T	p.Thr2326Thr	synonymous_variant	Exon 32 of 33	2		ENSP00000332265.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		0.20

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: rs2306058; hg19: chr4-73942678;