2-95908690-A-C

Variant names:

• chr2-95908690-A-C
• rs183934154
• NM_001393982.1:c.2865T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001393982.1(ANKRD36C):​c.2865T>G​(p.Ser955Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 1,553,192 control chromosomes in the GnomAD database, including 977 homozygotes. 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. S955S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.029 (123 hom., cov: 29)
  • Exomes 𝑓: 0.035 (854 hom.)
• Consequence: ANKRD36C NM_001393982.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 2 publications found

Genes affected

ANKRD36C (HGNC:32946): (ankyrin repeat domain 36C)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0295 (4452/151056) while in subpopulation NFE AF = 0.0341 (2297/67378). AF 95% confidence interval is 0.0329. There are 123 homozygotes in GnomAd4. There are 2072 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 123 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393982.1. 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
	ANKRD36C	NM_001393982.1	MANE Select	c.2865T>G	p.Ser955Ser	synonymous	Exon 47 of 88	NP_001380911.1	A0A8J8YUB5
	ANKRD36C	NM_001310154.3		c.2940T>G	p.Ser980Ser	synonymous	Exon 48 of 89	NP_001297083.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD36C	ENST00000295246.7	TSL:5 MANE Select	c.2865T>G	p.Ser955Ser	synonymous	Exon 47 of 88	ENSP00000295246.7	A0A8J8YUB5
	ANKRD36C	ENST00000456556.5	TSL:5	c.2653+3554T>G		intron	N/A	ENSP00000403302.1	Q5JPF3-1
	ANKRD36C	ENST00000534304.5	TSL:5	n.*981+3554T>G		intron	N/A	ENSP00000433685.1	H0YDI7

Frequencies

GnomAD3 genomes AF: 0.0295 AC: 4453 AN: 150938 Hom.: 123 Cov.: 29

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0514

Gnomad EAS AF: 0.0153

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0352

GnomAD2 exomes AF: 0.0302 AC: 4999 AN: 165748 AF XY: 0.0306

Gnomad AFR exome AF: 0.0232

Gnomad AMR exome AF: 0.0190

Gnomad ASJ exome AF: 0.0560

Gnomad EAS exome AF: 0.0209

Gnomad FIN exome AF: 0.0189

Gnomad NFE exome AF: 0.0373

Gnomad OTH exome AF: 0.0366

GnomAD4 exome AF: 0.0347 AC: 48723 AN: 1402136 Hom.: 854 Cov.: 32 AF XY: 0.0346 AC XY: 24006 AN XY: 693020

African (AFR) AF: 0.0219 AC: 695 AN: 31778

American (AMR) AF: 0.0200 AC: 747 AN: 37308

Ashkenazi Jewish (ASJ) AF: 0.0532 AC: 1330 AN: 25004

East Asian (EAS) AF: 0.0126 AC: 465 AN: 36884

South Asian (SAS) AF: 0.0285 AC: 2277 AN: 79934

European-Finnish (FIN) AF: 0.0179 AC: 895 AN: 49900

Middle Eastern (MID) AF: 0.0397 AC: 159 AN: 4002

European-Non Finnish (NFE) AF: 0.0370 AC: 39983 AN: 1079580

Other (OTH) AF: 0.0376 AC: 2172 AN: 57746

GnomAD4 genome AF: 0.0295 AC: 4452 AN: 151056 Hom.: 123 Cov.: 29 AF XY: 0.0281 AC XY: 2072 AN XY: 73754

African (AFR) AF: 0.0244 AC: 1010 AN: 41348

American (AMR) AF: 0.0298 AC: 452 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 177 AN: 3444

East Asian (EAS) AF: 0.0152 AC: 77 AN: 5076

South Asian (SAS) AF: 0.0304 AC: 145 AN: 4764

European-Finnish (FIN) AF: 0.0166 AC: 175 AN: 10560

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.0341 AC: 2297 AN: 67378

Other (OTH) AF: 0.0353 AC: 74 AN: 2096

Alfa AF: 0.0205 Hom.: 20

Bravo AF: 0.0313

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.33
PhyloP100		0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs183934154; hg19: chr2-96574438; COSMIC: COSV54758278; COSMIC: COSV54758278;