2-214955289-G-A

Variant names:

• chr2-214955289-G-A
• rs10498027
• NM_173076.3:c.6306C>T
• ABCA12 p.Tyr2102Tyr

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_173076.3(ABCA12):​c.6306C>T​(p.Tyr2102Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,613,548 control chromosomes in the GnomAD database, including 135,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11635 hom., cov: 33)
  • Exomes 𝑓: 0.41 (123378 hom.)
• Consequence: ABCA12 NM_173076.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.500
• Publications: 23 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-214955289-G-A is Benign according to our data. Variant chr2-214955289-G-A is described in ClinVar as Benign. ClinVar VariationId is 262831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173076.3. 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
	ABCA12	NM_173076.3	MANE Select	c.6306C>T	p.Tyr2102Tyr	synonymous	Exon 43 of 53	NP_775099.2
	ABCA12	NM_015657.4		c.5352C>T	p.Tyr1784Tyr	synonymous	Exon 35 of 45	NP_056472.2
	ABCA12	NR_103740.2		n.6804C>T		non_coding_transcript_exon	Exon 45 of 55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA12	ENST00000272895.12	TSL:1 MANE Select	c.6306C>T	p.Tyr2102Tyr	synonymous	Exon 43 of 53	ENSP00000272895.7	Q86UK0-1
	ABCA12	ENST00000389661.4	TSL:1	c.5352C>T	p.Tyr1784Tyr	synonymous	Exon 35 of 45	ENSP00000374312.4	Q86UK0-2
	SNHG31	ENST00000607412.2	TSL:2	n.474-6521G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58710 AN: 151908 Hom.: 11625 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.418

GnomAD2 exomes AF: 0.406 AC: 101921 AN: 251218 AF XY: 0.412

Gnomad AFR exome AF: 0.311

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.513

Gnomad EAS exome AF: 0.236

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.417

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.408 AC: 596543 AN: 1461522 Hom.: 123378 Cov.: 42 AF XY: 0.411 AC XY: 298803 AN XY: 727096

African (AFR) AF: 0.306 AC: 10243 AN: 33474

American (AMR) AF: 0.402 AC: 17969 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 13158 AN: 26134

East Asian (EAS) AF: 0.243 AC: 9661 AN: 39678

South Asian (SAS) AF: 0.472 AC: 40754 AN: 86254

European-Finnish (FIN) AF: 0.427 AC: 22820 AN: 53414

Middle Eastern (MID) AF: 0.430 AC: 2478 AN: 5768

European-Non Finnish (NFE) AF: 0.409 AC: 454705 AN: 1111706

Other (OTH) AF: 0.410 AC: 24755 AN: 60376

GnomAD4 genome AF: 0.386 AC: 58754 AN: 152026 Hom.: 11635 Cov.: 33 AF XY: 0.387 AC XY: 28744 AN XY: 74314

African (AFR) AF: 0.314 AC: 13007 AN: 41424

American (AMR) AF: 0.412 AC: 6304 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1781 AN: 3472

East Asian (EAS) AF: 0.243 AC: 1258 AN: 5176

South Asian (SAS) AF: 0.464 AC: 2237 AN: 4824

European-Finnish (FIN) AF: 0.410 AC: 4330 AN: 10560

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.417 AC: 28331 AN: 67974

Other (OTH) AF: 0.418 AC: 882 AN: 2112

Alfa AF: 0.410 Hom.: 26367

Bravo AF: 0.378

Asia WGS AF: 0.356 AC: 1239 AN: 3478

EpiCase AF: 0.422

EpiControl AF: 0.418

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Autosomal recessive congenital ichthyosis 4A (1)
-	-	1	Autosomal recessive congenital ichthyosis 4B (1)
-	-	1	Congenital ichthyosis of skin (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.11
DANN	Benign	0.37
PhyloP100		-0.50
Mutation Taster		=99/1	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10498027;

hg19: chr2-215820013;

COSMIC: COSV55978073;