2-95855406-C-T

Variant names:

• chr2-95855406-C-T
• rs77972623
• NM_001393982.1:c.5878G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393982.1(ANKRD36C):​c.5878G>A​(p.Asp1960Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1960H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ANKRD36C NM_001393982.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

Genes affected

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

ENSG00000290897 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08229798).

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.5878G>A	p.Asp1960Asn	missense	Exon 83 of 88	NP_001380911.1	A0A8J8YUB5
	ANKRD36C	NM_001310154.3		c.5953G>A	p.Asp1985Asn	missense	Exon 84 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.5878G>A	p.Asp1960Asn	missense	Exon 83 of 88	ENSP00000295246.7	A0A8J8YUB5
	ANKRD36C	ENST00000488721.5	TSL:1	n.1028G>A		non_coding_transcript_exon	Exon 3 of 4
	ANKRD36C	ENST00000456556.5	TSL:5	c.4855G>A	p.Asp1619Asn	missense	Exon 63 of 67	ENSP00000403302.1	Q5JPF3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461186 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726874

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111620

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.00071	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.94	T
PhyloP100		1.5
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.059
Sift	Benign	0.15	T
Sift4G	Benign	0.11	T
Vest4		0.063
MutPred		0.17		Gain of MoRF binding (P = 0.0301)
MVP		0.076
ClinPred		0.17	T
GERP RS		-0.83
PromoterAI		-0.0088	Neutral
Varity_R		0.040
gMVP		0.0094
Mutation Taster		=99/1	polymorphism

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: rs77972623; hg19: chr2-96521154;