10-97578365-C-G

Variant names:

• chr10-97578365-C-G
• rs140040097
• NM_001346793.2:c.315C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001346793.2(ANKRD2):​c.315C>G​(p.Ala105Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000812 in 1,613,670 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00084 (1 hom.)
• Consequence: ANKRD2 NM_001346793.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0670
• Publications: 0 publications found

Genes affected

ANKRD2 (HGNC:495): (ankyrin repeat domain 2) This gene encodes a protein that belongs to the muscle ankyrin repeat protein (MARP) family. A similar gene in rodents is a component of a muscle stress response pathway and plays a role in the stretch-response associated with slow muscle function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 10-97578365-C-G is Benign according to our data. Variant chr10-97578365-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2640739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.067 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346793.2. 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
	ANKRD2	NM_001346793.2	MANE Select	c.315C>G	p.Ala105Ala	synonymous	Exon 3 of 9	NP_001333722.1	A0A0A0MRN9
	ANKRD2	NM_001291218.2		c.654C>G	p.Ala218Ala	synonymous	Exon 3 of 9	NP_001278147.1
	ANKRD2	NM_020349.4		c.396C>G	p.Ala132Ala	synonymous	Exon 3 of 9	NP_065082.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD2	ENST00000370655.6	TSL:1 MANE Select	c.315C>G	p.Ala105Ala	synonymous	Exon 3 of 9	ENSP00000359689.1	A0A0A0MRN9
	ANKRD2	ENST00000307518.9	TSL:1	c.396C>G	p.Ala132Ala	synonymous	Exon 3 of 9	ENSP00000306163.5	Q9GZV1-1
	ANKRD2	ENST00000298808.9	TSL:1	c.396C>G	p.Ala132Ala	synonymous	Exon 3 of 8	ENSP00000298808.5	Q9GZV1-2

Frequencies

GnomAD3 genomes AF: 0.000500 AC: 76 AN: 152064 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000325 AC: 81 AN: 249600 AF XY: 0.000310

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000676

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000845 AC: 1235 AN: 1461606 Hom.: 1 Cov.: 35 AF XY: 0.000761 AC XY: 553 AN XY: 727122

African (AFR) AF: 0.000120 AC: 4 AN: 33472

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00101 AC: 1120 AN: 1111916

Other (OTH) AF: 0.00177 AC: 107 AN: 60378

GnomAD4 genome AF: 0.000500 AC: 76 AN: 152064 Hom.: 0 Cov.: 31 AF XY: 0.000444 AC XY: 33 AN XY: 74270

African (AFR) AF: 0.000169 AC: 7 AN: 41424

American (AMR) AF: 0.0000655 AC: 1 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000985 AC: 67 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000469 Hom.: 0

Bravo AF: 0.000540

EpiCase AF: 0.000872

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.0
DANN	Benign	0.67
PhyloP100		0.067

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: rs140040097; hg19: chr10-99338122;