2-95855406-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001393982.1(ANKRD36C):​c.5878G>C​(p.Asp1960His) variant causes a missense 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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD36C NM_001393982.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 1.51

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0040079057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36C	NM_001393982.1	c.5878G>C	p.Asp1960His	missense_variant	Exon 83 of 88	ENST00000295246.7	NP_001380911.1
ANKRD36C	NM_001310154.3	c.5953G>C	p.Asp1985His	missense_variant	Exon 84 of 89		NP_001297083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD36C	ENST00000295246.7	c.5878G>C	p.Asp1960His	missense_variant	Exon 83 of 88	5	NM_001393982.1	ENSP00000295246.7
ANKRD36C	ENST00000488721.5	n.1028G>C		non_coding_transcript_exon_variant	Exon 3 of 4	1
ANKRD36C	ENST00000456556.5	c.4855G>C	p.Asp1619His	missense_variant	Exon 63 of 67	5		ENSP00000403302.1
ANKRD36C	ENST00000612359.4	c.-69G>C		upstream_gene_variant		1		ENSP00000485004.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0406 Hom.: 0

ExAC AF: 0.0244 AC: 2960

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Peritoneal Gliomatosis Uncertain:1

Aug 01, 2019

Treehouse Childhood Cancer Initiative, UC Santa Cruz

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Uncertain:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.61
DEOGEN2	Benign	0.00075	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.94	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.033
Sift	Benign	0.29	T
Sift4G	Uncertain	0.0060	D
Vest4		0.043
ClinPred		0.011	T
GERP RS		-0.83
Varity_R		0.044
gMVP		0.022

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

Publications

LitVar

Other links and lift over

dbSNP: rs77972623; hg19: chr2-96521154; COSMIC: COSV69431234; COSMIC: COSV69431234;