4-73077438-G-T

Variant names:

• chr4-73077438-G-T
• rs1953365097
• NM_032217.5:c.7504C>A

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.7504C>A​(p.Arg2502Arg) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD17 NM_032217.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• 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):

• 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

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=-0.42).
• BP7: Synonymous conserved (PhyloP=1.74 with no splicing effect.

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.7504C>A	p.Arg2502Arg	synonymous	Exon 32 of 34	NP_115593.3
	ANKRD17	NM_015574.2		c.7501C>A	p.Arg2501Arg	synonymous	Exon 32 of 34	NP_056389.1	O75179-2
	ANKRD17	NM_001286771.3		c.7165C>A	p.Arg2389Arg	synonymous	Exon 32 of 34	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.7504C>A	p.Arg2502Arg	synonymous	Exon 32 of 34	ENSP00000351416.4	O75179-1
	ANKRD17	ENST00000509867.6	TSL:1	c.7165C>A	p.Arg2389Arg	synonymous	Exon 32 of 34	ENSP00000427151.2	O75179-7
	ANKRD17	ENST00000558247.5	TSL:1	c.7153C>A	p.Arg2385Arg	synonymous	Exon 32 of 34	ENSP00000453434.1	H0YM23

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.5
DANN	Benign	0.63
PhyloP100		1.7

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: rs1953365097; hg19: chr4-73943155;