2-214948607-C-T

Position:

chr2-214948607-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000272895.12(ABCA12):c.7093G>A(p.Asp2365Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,613,738 control chromosomes in the GnomAD database, including 802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 69 hom., cov: 31)

Exomes 𝑓: 0.028 ( 733 hom. )

Consequence

ABCA12
ENST00000272895.12 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:8

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

ABCA12 (HGNC:14637): (ATP binding cassette subfamily A member 12) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily, which is the only major ABC subfamily found exclusively in multicellular eukaryotes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ABCA12 links:

SNHG31 (HGNC:54196): (small nucleolar RNA host gene 31)

SNHG31 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023857653).

BP6

Variant 2-214948607-C-T is Benign according to our data. Variant chr2-214948607-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-214948607-C-T is described in Lovd as [Likely_benign]. Variant chr2-214948607-C-T is described in Lovd as [Pathogenic].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3468/152196) while in subpopulation NFE AF= 0.029 (1969/68006). AF 95% confidence interval is 0.0279. There are 69 homozygotes in gnomad4. There are 1841 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 69 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA12	NM_173076.3 linkuse as main transcript	c.7093G>A	p.Asp2365Asn	missense_variant	47/53	ENST00000272895.12	NP_775099.2
SNHG31	NR_110292.1 linkuse as main transcript	n.444+660C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA12	ENST00000272895.12 linkuse as main transcript	c.7093G>A	p.Asp2365Asn	missense_variant	47/53	1	NM_173076.3	ENSP00000272895	P1	Q86UK0-1
SNHG31	ENST00000670391.1 linkuse as main transcript	n.438-13203C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3471

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00560

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0289

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0279

AC:

7024

AN:

251338

Hom.:

165

AF XY:

0.0273

AC XY:

3710

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00468

Gnomad AMR exome

AF:

0.0279

Gnomad ASJ exome

AF:

0.00774

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0162

Gnomad FIN exome

AF:

0.0800

Gnomad NFE exome

AF:

0.0311

Gnomad OTH exome

AF:

0.0224

GnomAD4 exome

AF:

0.0284

AC:

41537

AN:

1461542

Hom.:

733

Cov.:

AF XY:

0.0283

AC XY:

20586

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00409

Gnomad4 AMR exome

AF:

0.0252

Gnomad4 ASJ exome

AF:

0.00708

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0160

Gnomad4 FIN exome

AF:

0.0753

Gnomad4 NFE exome

AF:

0.0299

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.0228

AC:

3468

AN:

152196

Hom.:

Cov.:

AF XY:

0.0247

AC XY:

1841

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00559

Gnomad4 AMR

AF:

0.0125

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0853

Gnomad4 NFE

AF:

0.0290

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0254

Hom.:

150

Bravo

AF:

0.0171

TwinsUK

AF:

0.0280

AC:

104

ALSPAC

AF:

0.0252

AC:

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.0259

AC:

223

ExAC

AF:

0.0278

AC:

3369

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0252

EpiControl

AF:

0.0251

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	ABCA12: BP4, BS1, BS2; SNHG31: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Autosomal recessive congenital ichthyosis 4B

Pathogenic:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	May 01, 2005	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Congenital ichthyosis of skin

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive congenital ichthyosis 4B;C1832550:Autosomal recessive congenital ichthyosis 4A

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;.

Eigen

Benign

-0.024

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

A;A

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.2

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.28

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.91

P;B

Vest4

0.093

MPC

0.61

ClinPred

0.026

GERP RS

4.6

Varity_R

0.15

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over